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Guidelines for the Use of Antiretroviral Agents in
Adults and Adolescents Living with HIV
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Guidelines Development Process
Table 1. Outline of the Guidelines Development Process
Topic Comment
Goal of the guidelines Provide guidance to HIV care practitioners on the optimal use of antiretroviral agents (ARVs) for the
treatment of HIV in adults and adolescents in the United States.
Panel members The Panel is composed of approximately 45 voting members who have expertise in HIV care and
research, and includes at least one representative from each of the following U.S. Department of Health
and Human Services (HHS) agencies: Centers for Disease Control and Prevention (CDC), Food and
Drug Administration (FDA), Health Resource Services Administration (HRSA), and National Institutes of
Health (NIH). Approximately two-thirds of the Panel members are nongovernmental scientific members.
The Panel also includes four to five community members with knowledge in HIV treatment and care.
The U.S. government representatives are appointed by their respective agencies; other Panel members
are selected after an open announcement to call for nominations. Each member serves on the Panel for
a 4 year term with an option for reappointment for an additional term. See the Panel Roster for a list of
current Panel members.
Financial disclosure All members of the Panel submit a written financial disclosure annually, reporting any association
with manufacturers of ARV drugs or diagnostics used for management of HIV infections. A list of
the latest disclosures is available on the AIDSinfo website (http://aidsinfo.nih.gov/contentfiles/AA_
FinancialDisclosures.pdf).
Users of the guidelines HIV treatment providers
Developer Panel on Antiretroviral Guidelines for Adults and Adolescents—a working group of the Office of AIDS
Research Advisory Council (OARAC)
Funding source Office of AIDS Research, NIH
Evidence collection The recommendations in the guidelines are based on studies published in peer reviewed journals.
On some occasions, particularly when new information may affect patient safety, unpublished data
presented at major conferences or prepared by the FDA and/or manufacturers as warnings to the public
may be used as evidence to revise the guidelines.
Recommendation grading As described in Table 2
Method of synthesizing data Each section of the guidelines is assigned to a working group of Panel members with expertise in the
section’s area of interest. The working groups synthesize available data and propose recommendations
to the Panel. The Panel discusses all proposals during monthly teleconferences. Recommendations
endorsed by the Panel are included in the guidelines.
Other guidelines These guidelines focus on antiretroviral therapy (ART) use for adults and adolescents with HIV. For
more detailed discussion on the use of ART for children and prepubertal adolescents (SMR I – III),
clinicians should refer to the Pediatric ARV Guidelines.
These guidelines also include a brief discussion on the management of women of reproductive age and
pregnant women.
Update plan The Panel meets monthly by teleconference to review data that may warrant modification of the
guidelines. Updates may be prompted by new drug approvals (or new indications, dosing formulations,
or frequency of dosing), new safety or efficacy data, or other information that may have an impact on the
clinical care of patients. In the event of new data of clinical importance, the Panel may post an interim
announcement with recommendations on the AIDSinfo website until the guidelines can be updated with
the appropriate changes. Updated guidelines are available on the AIDSinfo website (http://www.aidsinfo.
nih.gov).
Public comments A 2-week public comment period follows release of the updated guidelines on the AIDSinfo website.
The Panel reviews comments received to determine whether additional revisions to the guidelines are
indicated. The public may also submit comments to the Panel at any time at contactus@aidsinfo.nih.
gov.
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV 1

Table 2. Rating Scheme for Recommendations
Strength of Recommendationi Quality of Evidence for Recommendation

A: Strong recommendation for the statement I: One or more randomized trials with clinical outcomes and/or
validated laboratory endpoints
B: Moderate recommendation for the statement
II: One or more well-designed, non-randomized trials or
C: Optional recommendation for the statement observational cohort studies with long-term clinical
outcomes
III: Expert opinion

Table 3. Laboratory Testing Schedule for Monitoring Patients with HIV Before and After Initiation of Antiretroviral Therapya (page 1 of 3)
Timepoint or Frequency of Testing
2 to 8 Weeks
Laboratory Test ART
Entry into After ART Every 3 to 6 Treatment Clinically If ART Initiation is
Initiationb or Every 6 Months Every 12 Months
Care Initiation or Months Failure Indicated Delayedc
Modification
Modification
HIV Serology √
If HIV
diagnosis
has not
been
confirmed
CD4 Count √ √ √ √ √ √ √
During first 2 years After 2 Years on ART Every 3–6 months
of ART, or if viremia with Consistently
develops while Suppressed Viral
patient is on ART, Load:
or if CD4 count is CD4 Count 300–500
<300 cells/mm3 cells/mm3:
• Every 12 months
CD4 Count >500 cells/
mm3:
• CD4 monitoring is
optional.
HIV Viral Load √ √ √d √e √e √ √ Repeat testing is
optional.
Resistance √ √f √ √ √f
Testing
HLA-B*5701 √
Testing If considering
ABC
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV C-2
2 to 8 Weeks
Laboratory Test ART
Modification
Modification
Tropism Testing √ √ √
If considering If considering
a CCR5 a CCR5
antagonist antagonist, or
for patients
experiencing
virologic
failure on
a CCR5
antagonist-
based
regimen
Hepatitis B √ √ √ √
Serology May repeat May repeat if patient is Including
(HBsAb, HBsAg, if patient is nonimmune and does prior to
HBcAb total)g,h,i nonimmune not have chronic HBV starting HCV
and does not infectionh DAA (see
have chronic HCV/HIV
HBV infectionh Coinfection)
Hepatitis C √ √ √
Screening Repeat HCV screening
(HCV antibody or, for at-risk patientsk
if indicated, HCV
RNA)j
Basic √ √ √ √ √ √
Chemistryl,m Every 6–12 months
ALT, AST, Total √ √ √ √ √ √
Bilirubin Every 6–12 months
CBC with √ √ √ √ √ √ √
Differential If on ZDV If on ZDV or if CD4 Every 3–6 months
testing is done
2 to 8 Weeks
Laboratory Test ART
Modification
Modification
Fasting Lipid √ √ √ √ √ √
Profilen If abnormal If normal at last If normal at
at last measurement baseline, annually
measurement
Fasting Glucose √ √ √ √ √ √
or Hemoglobin If abnormal at last If normal at last If normal at
A1C measurement measurement baseline, annually
Urinalysism,o √ √ √ √ √
If on TAF or TDF l
Pregnancy Test p
√ √ √
a
his table pertains to laboratory tests done to select an ARV regimen and monitor for treatment responses or ART toxicities. Please refer to the HIV Primary Care Guidelines for guidance on other
T
laboratory tests generally recommended for primary health care maintenance of HIV patients.1
b
If ART initiation occurs soon after HIV diagnosis and entry into care, repeat baseline laboratory testing is not necessary.
c
RT is indicated for all individuals with HIV and should be started as soon as possible. However, if ART initiation is delayed, patients should be retained in care, with periodic monitoring as noted
A
above.
d
If HIV RNA is detectable at 2 to 8 weeks, repeat testing every 4 to 8 weeks until viral load is suppressed to <200 copies/mL. Thereafter, repeat testing every 3 to 6 months.
e
In patients on ART, viral load typically is measured every 3 to 4 months. However, for adherent patients with consistently suppressed viral load and stable immunologic status for more than 2 years,
monitoring can be extended to 6-month intervals.
f
ased on current rates of transmitted drug resistance to different ARV medications, standard genotypic drug-resistance testing in ARV-naive persons should focus on testing for mutations in
B
the reverse transcriptase and protease genes. If transmitted INSTI resistance is a concern, providers should also test for resistance mutations to this class of drugs. In ART-naive patients who
do not immediately begin ART, repeat testing before initiation of ART is optional if resistance testing was performed at entry into care. In patients with virologic suppression who are switching
therapy because of toxicity or for convenience, viral amplification will not be possible; therefore, resistance testing should not be performed. Results from prior resistance testing can be helpful in
constructing a new regimen.
g
If patient has HBV infection (as determined by a positive HBsAg or HBV DNA test result), TDF or TAF plus either FTC or 3TC should be used as part of the ARV regimen to treat both HBV and HIV
infections.
h
If HBsAg, HBsAb, and HBcAb test results are negative, hepatitis B vaccine series should be administered. Refer to the HIV Primary Care Guidelines and the Adult and Adolescent Opportunistic
Infections Guidelines for detailed recommendations.1,2
i
ost patients with isolated HBcAb have resolved HBV infection with loss of HBsAb. Consider performing an HBV viral load for confirmation. If the HBV viral load is positive, the patient may be
M
acutely infected (and will usually display other signs of acute hepatitis) or chronically infected. If negative, the patient should be vaccinated. Refer to the HIV Primary Care Guidelines and the Adult
and Adolescent Opportunistic Infections Guidelines for more detailed recommendations.1,2
j
he HCV antibody test may not be adequate for screening in the setting of recent HCV infection (defined as acquisition within the past 6 months), or advanced immunodeficiency (CD4
T
count <100 cells/mm3). HCV RNA screening is indicated in persons who have been successfully treated for HCV or who spontaneously cleared prior infection. HCV antibody-negative
patients with elevated ALT may need HCV RNA testing.
k
Injection drug users, persons with a history of incarceration, men with HIV who have unprotected sex with men, and persons with percutaneous/parenteral exposure to blood in unregulated
settings are at risk of HCV infection.
l
Serum Na, K, HCO3, Cl, BUN, creatinine, glucose (preferably fasting), and creatinine-based estimated glomerular filtration rate. Serum phosphorus should be monitored in patients with
chronic kidney disease who are on TAF- or TDF-containing regimens.3
m
onsult the Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society
C
of America for recommendations on managing patients with renal disease.3 More frequent monitoring may be indicated for patients with evidence of kidney disease (e.g., proteinuria,
decreased glomerular dysfunction) or increased risk of renal insufficiency (e.g., patients with diabetes, hypertension).
n
Consult the National Lipid Association’s recommendations for management of patients with dyslipidemia.4
o
Urine glucose and protein should be assessed before initiating TAF- or TDF-containing regimens and monitored during treatment with these regimens.
p
This applies to people of childbearing potential.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; BUN =
blood urea nitrogen; CBC = complete blood count; CD4 = CD4 T lymphocyte; Cl = chloride; DAA = direct-acting antiviral; FTC = emtricitabine; HBcAb = hepatitis B core antibody; HBsAb
= hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCO3 = bicarbonate; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; K =
potassium; Na = sodium; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine
Table 4. Recommendations on the Indications and Frequency of Viral Load and CD4 Count Monitoringa
Clinical Scenario Viral Load Monitoring CD4 Count Monitoring

Before initiating ART At entry into care (AIII) At entry into care (AI)
If ART initiation is deferred, repeat before If ART is deferred, every 3 to 6 monthsb
initiating ART (AIII). (AIII)
In patients not initiating ART, repeat testing is
optional (CIII).
After initiating ART Preferably within 2 to 4 weeks (and no later than 3 months after initiation of ART (AIII)
8 weeks) after initiation of ART (AIII); thereafter,
every 4 to 8 weeks until viral load is suppressed
(BIII).
After modifying ART because of drug 4 to 8 weeks after modification of ART to confirm Monitor according to prior CD4 count and
toxicities or for regimen simplification in effectiveness of new regimen (AIII). duration on ART, as outlined below.
a patient with viral suppression
After modifying ART because of Preferably within 2 to 4 weeks (and no later than Every 3 to 6 months (AI)
virologic failure 8 weeks) after modification (AIII); thereafter,
every 4 to 8 weeks until viral load is suppressed
(BIII). If viral suppression is not possible, repeat
viral load every 3 months or more frequently if
indicated (AIII).
During the first 2 years of ART Every 3 to 4 months (AIII) Every 3 to 6 monthsa (BII)
After 2 years of ART (VL consistently Every 12 months (BII)
suppressed, CD4 consistently 300-500
cells/mm3) Can extend to every 6 months for patients with
After 2 years of ART (VL consistently consistent viral suppression for ≥2 years (AIII). Optional (CIII)
suppressed, CD4 consistently >500
cells/mm3)
While on ART with detectable viremia Every 3 months (AIII) or more frequently if Every 3 to 6 months (AIII)
(VL repeatedly >200 copies/mL) clinically indicated (see Virologic Failure).
Change in clinical status (e.g., new Every 3 months (AIII) Perform CD4 count and repeat as
HIV clinical symptom or initiation clinically indicatedc (AIII)
of interferon, chronic systemic
corticosteroids, or antineoplastic
therapy)
a
onitoring of lymphocyte subsets other than CD4 (e.g., CD8, CD19) has not proven clinically useful, adds to costs, and is not routinely
M
recommended (BIII).
b
ome experts may repeat CD4 count every 3 months in patients with low baseline CD4 count (<200–300 cells/mm3) before ART but
S
every 6 months in those who initiated ART at higher CD4 cell count (e.g., >300 cells/mm3).
c
he following are examples of clinically indicated scenarios: changes in a patient’s clinical status that may decrease CD4 count and thus
T
prompt initiation of prophylaxis for opportunistic infections (OI), such as new HIV-associated symptoms, or initiation of treatment with
medications which are known to reduce CD4 cell count.

Table 5. Recommendations for Using Drug-Resistance Assays (page 1 of 2)
Clinical Setting and Recommendation Rationale
In Acute or Recent (Early) HIV Infection: Drug-resistance testing can determine whether drug-resistant
Drug-resistance testing is recommended (AII). A genotypic assay virus was transmitted. The initial regimen can be modified, if
is generally preferred (AIII). Treatment should not be delayed while necessary, once resistance test results are available. Genotypic
awaiting results of resistance testing (AIII). testing is preferred to phenotypic testing because of lower cost,
faster turnaround time, and greater sensitivity for detecting
mixtures of wild-type and resistant virus.
If ART is deferred, repeat resistance testing may be considered Repeat testing when ART is initiated may be considered because
when therapy is initiated (CIII). A genotypic assay is generally the patient may have acquired a drug-resistant virus (i.e.,
preferred (AIII). superinfection).
In ART-Naive Patients with Chronic HIV: Transmitted HIV with baseline resistance to at least 1 drug is seen
Drug-resistance testing is recommended at entry into HIV care to in 10% to 17% of patients, and suboptimal virologic responses
guide selection of initial ART (AII). A genotypic assay is generally may be seen in patients with baseline resistant mutations to ARVs
preferred (AIII). in the prescribed regimen. Some drug-resistance mutations can
remain detectable for years in untreated patients with chronic HIV.
For pregnant persons, or if ART will be initiated on the day of If necessary, the ART regimen can be modified once resistance
or soon after HIV diagnosis, treatment can be initiated prior to test results are available.
receiving resistance testing results.
If an INSTI is considered for an ART-naive patient and/or Genotypic assays provide information on resistance to NRTIs,
transmitted INSTI resistance is a concern, providers should NNRTIs, PIs, and INSTIs. In some circumstances, INSTI
supplement standard resistance testing with a specific INSTI resistance tests need to be ordered separately (clinicians should
genotypic resistance assay, which may need to be ordered check with the testing laboratory). Currently, transmitted INSTI
separately (AIII). resistance is infrequent, but the risk of a patient acquiring INSTI-
resistant strains may be greater in certain known exposure
settings.
If therapy is deferred, repeat resistance testing may be considered Repeat testing before initiation of ART may be considered
before initiation of ART (CIII). A genotypic assay is generally because the patient may have acquired a drug-resistant virus (i.e.,
preferred (AIII). a superinfection).
Genotypic testing is preferred to phenotypic testing because
of lower cost, faster turnaround time, and greater sensitivity for
detecting mixtures of wild-type and resistant virus.
If use of a CCR5 antagonist is being considered, a co-receptor See Co-Receptor Tropism Assays section.
tropism assay should be performed (AI).
In Patients with Virologic Failure: Drug-resistance testing can help determine the role of resistance
Drug-resistance testing is recommended in patients on combination in drug failure and maximize the clinician’s ability to select active
ART with HIV RNA levels >1,000 copies/mL (AI). In patients with drugs for the new regimen.
HIV RNA levels >500 copies/mL but <1,000 copies/mL, testing may
not be successful but should still be considered (BII).
Resistance testing should be done while the patient is taking ART The absence of detectable resistance in such patients must
or, if that is not possible, within 4 weeks after ART discontinuation be interpreted with caution when designing subsequent ARV
(AII). If >4 weeks have elapsed, resistance testing may still be regimens, as mutations may decay with time.
useful to guide therapy; however, previously-selected mutations
can be missed due to lack of drug selective pressure (CIII).
A standard genotypic resistance assay is generally preferred Genotypic testing is preferred to phenotypic testing because
for patients experiencing virologic failure on their first or second of lower cost, faster turnaround time, and greater sensitivity for
regimens and for those with noncomplex resistance patterns (AII). detecting mixtures of wild-type and resistant HIV.
All prior and current drug-resistance testing results should be Drug resistance mutations may decay with time, and mutations
reviewed and considered when designing a new regimen for a detected in prior resistance tests may not be detected in current
patient experiencing virologic failure (AIII). tests, though they remain clinically relevant.
When virologic failure occurs while a patient is on an INSTI- Genotypic assays provide information on resistance to NRTI-,
based regimen, genotypic testing for INSTI resistance should be NNRTI-, PI-, and INSTI-associated mutations. In some
performed to determine whether to include drugs from this class in circumstances, INSTI resistance tests need to be ordered
subsequent regimens (AII). separately (clinicians should check with the testing laboratory).

Table 5. Recommendations for Using Drug-Resistance Assays (page 2 of 2)
Clinical Setting and Recommendation Rationale
Adding phenotypic testing to genotypic testing is generally Phenotypic testing can provide additional useful information in
preferred in patients with known or suspected complex drug- patients with complex drug resistance mutation patterns.
resistance patterns (BIII).
In Patients with Suboptimal Suppression of Viral Load: Testing can determine the role of resistance in suboptimal viral
Drug-resistance testing is recommended in patients with suboptimal suppression, and it can help the clinician identify the number of
viral load suppression after initiation of ART (AII). active drugs available in the current regimen and assess the need
for a new regimen.
In Pregnant Persons with HIV: The goals of ART in pregnant persons with HIV are to achieve
Genotypic resistance testing is recommended for all pregnant maximal viral suppression for treatment of maternal HIV and to
persons before initiation of ART (AIII) and for those entering prevent perinatal transmission of HIV. Genotypic resistance testing
pregnancy with detectable HIV RNA levels while on therapy (AI). will assist the clinician in selecting the optimal regimen for the
patient. However, treatment should not be delayed while awaiting
results of resistance testing. The initial regimen can be modified
once resistance test results are available, if needed.
In Patients with Undetectable Viral Load or Low-Level Viremia: This test may provide information about previously circulating
HIV-1 proviral DNA resistance assays may be useful in patients resistant viral variants that are archived within proviral DNA.
with HIV RNA below the limit of detection or with low-level viremia, These assays may miss some or all prior resistance mutations
where a HIV RNA genotypic assay is unlikely to be successful that have occurred within the viral quasi-species, and therefore
(CIII). they should be interpreted with caution. The clinical utility of HIV-1
proviral DNA assays has not been fully determined.
Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; INSTI = integrase strand transfer inhibitors; NNRTI = non-nucleoside
reverse-transcriptase inhibitors; NRTI = nucleoside reverse-transcriptase inhibitors; PI = protease inhibitor

Table 6a. Recommended Antiretroviral Regimens for Initial Therapy (page 1 of 2)
Selection of a regimen should be individualized based on virologic efficacy, potential adverse effects,
childbearing potential and use of effective contraception, pill burden, dosing frequency, drug-drug interaction
potential, comorbid conditions, cost, access, and resistance test results. Drug classes and regimens within
each class are arranged first by evidence rating, and, when ratings are equal, in alphabetical order. Table 7
provides ARV recommendations based on specific clinical scenarios.
Recommended Initial Regimens for Most People with HIV
Recommended regimens are those with demonstrated durable virologic efficacy, favorable tolerability and toxicity profiles, and ease of use.
INSTI plus 2 NRTIs:
Note: For individuals of childbearing potential, see Table 6b before prescribing one of these regimens.
• BIC/TAF/FTC (AI)
• DTG/ABC/3TCa (AI)—if HLA-B*5701 negative
•D TG plus tenofovirb/FTCa (AI for both TAF/FTC and TDF/FTC)
• RALc plus tenofovirb/FTCa (BI for TDF/FTC, BII for TAF/FTC)
Recommended Initial Regimens in Certain Clinical Situations
These regimens are effective and tolerable but have some disadvantages when compared with the regimens listed above or have less
supporting data from randomized clinical trials. However, in certain clinical situations, one of these regimens may be preferred (see Table
7 for examples).
INSTI plus 2 NRTIs:
Note: For individuals of childbearing potential, see Table 6b before prescribing one of these regimens.
• EVG/c/tenofovirb/FTC (BI for both TAF/FTC and TDF/FTC)
• RALc plus ABC/3TCa (CII)—if HLA-B*5701 negative and HIV RNA <100,000 copies/mL
Boosted PI plus 2 NRTIs: (In general, boosted DRV is preferred over boosted ATV)
• (DRV/c or DRV/r) plus tenofovirb/FTCa (AI)
• (ATV/c or ATV/r) plus tenofovirb/FTCa (BI)
• (DRV/c or DRV/r) plus ABC/3TCa —if HLA-B*5701 negative (BII)
NNRTI plus 2 NRTIs:
• DOR/TDFb/3TC (BI) or DOR plus TAFb/FTC (BIII)
• EFV plus TDFb/FTCa (BI for EFV 600 mg/TDF/FTC or EFV 600 mg/TDF/3TC, BII for EFV 600 mg plus TAF/FTC)
• RPV/tenofovirb/FTCa (BI)—if HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3
Regimens to Consider when ABC, TAF, and TDF Cannot be Used or Are Not Optimal:
• DTG plus 3TC (BI)
• DRV/r plus RAL BID (CI)—if HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3
• DRV/r once daily plus 3TCa (CI)
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials, observational cohort
studies with long-term clinical outcomes, relative bioavailability/bioequivalence studies, or regimen comparisons from randomized switch
studies; III = Expert opinion
Note: The following are available as coformulated drugs: ABC/3TC, ATV/c, BIC/TAF/FTC, DOR/TDF/3TC, DRV/c, DRV/c/TAF/FTC, DTG/
ABC/3TC, EFV 600 mg/TDF/3TC, EFV/TDF/FTC, EVG/c/TAF/FTC, EVG/c/TDF/FTC, RPV/TAF/FTC, RPV/TDF/FTC, TAF/FTC, TDF/3TC,
and TDF/FTC.
a
3 TC may be substituted for FTC, or vice versa. ABC/3TC, TDF/3TC, TDF/FTC, and TAF/FTC are available as coformulated, two-NRTI
tablets, and they are also available as part of various STRs. Cost, access, and availability of STR formulations are among the factors to
consider when choosing between 3TC and FTC.
b
AF and TDF are two forms of tenofovir approved by the FDA. TAF has fewer bone and kidney toxicities than TDF, while TDF is
T
associated with lower lipid levels. Safety, cost, and access are among the factors to consider when choosing between these drugs.
c
RAL can be given as RAL 400 mg BID or RAL 1200 mg (two, 600-mg tablets) once daily.

Table 6a. Recommended Antiretroviral Regimens for Initial Therapy (page 2 of 2)
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c =
atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; BID = twice daily; CD4 = CD4 T lymphocyte; DOR = doravirine; DRV
= darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; EVG/c
= elvitegravir/cobicistat; FDA = Food and Drug Administration; FTC = emtricitabine; HLA = human leukocyte antigen; INSTI = integrase
strand transfer inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI =
protease inhibitor; RAL = raltegravir; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil
fumarate
Table 6b. Considerations Before Initiating Dolutegravir and Other Integrase Strand Transfer
Inhibitors as Initial Therapy
Pregnancy testing should be performed in those of childbearing potential prior to initiation of ART (AIII). Preliminary data suggest that
there is an increased risk of NTDs in infants born to women who were receiving DTG at the time of conception.6,7
Before Initiating DTG:
•P
roviders and people of childbearing potential should discuss the benefits and risks of using DTG, including the possible risk of NTDs;
appropriate counseling should be provided so that the individual can make an informed decision about the use of this drug (AIII).
• DTG should not be prescribed for individuals:
ho are pregnant and within 12 weeks post-conception (AII); or
•W
• Who are of childbearing potential and planning to become pregnant (AII); or
• Who are of childbearing potential, sexually active, and not using effective contraception (AIII).
• For those who are using effective contraception, a DTG-based regimen can be considered after weighing the risks and benefits of DTG
use with the individual (BIII).
• It is not yet known whether other INSTIs pose a similar risk of NTDs (i.e., a class effect).
• The chemical structure of BIC is similar to DTG. There are no safety data on the use of BIC around the time of conception. For those
who are of childbearing potential, but who are not pregnant, an approach similar to that outlined for DTG should be discussed before
considering the use of BIC-containing ART (AIII).
• In a person who is pregnant, BIC is not recommended because of insufficient safety data (AIII).
• In a person who is pregnant, EVG/c is also not recommended because low EVG concentrations have been reported when this drug is
given during the second and third trimesters (AII).13
• Among those who received RAL during pregnancy, the rate of fetal malformations is within the expected range for pregnancy outcomes
in the United States; however, data on RAL use during the first trimester is limited to fewer than 300 deliveries. As it is currently not
known whether the association between DTG and NTDs represents a class effect, this potential risk should be discussed with people of
childbearing potential who prefer an INSTI-containing regimen.
Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials, observational cohort
studies with long-term clinical outcomes, relative bioavailability/bioequivalence studies, or regimen comparisons from randomized switch
studies; III = Expert opinion
Key to Acronyms: ART = antiretroviral therapy; BIC = bictegravir; DTG = dolutegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase
strand transfer inhibitor; NTD = neural tube defect; RAL = raltegravir

Table 7. Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical Scenarios
(page 1 of 4)
This table provides guidance to clinicians in choosing an initial ARV regimen according to various patient
and regimen characteristics and specific clinical scenarios. When more than one scenario applies to a person
with HIV, clinicians should review considerations for each relevant scenario and use their clinical judgment
to select the most appropriate regimen. This table is intended to guide the initial choice of regimen. However,
if a person is doing well on a particular regimen, it is not necessary to switch to another regimen based on the
scenarios outlined in this table. Please see Table 9 for additional information regarding the advantages and
disadvantages of particular ARV medications.
Note: Preliminary data suggest that there may be an increased risk of NTDs in infants born to those who were
receiving DTG at the time of conception.6,7 Until more information is available, clinicians should review Table
6b for further guidance before prescribing an INSTI to a person of childbearing potential.
Patient or
Regimen Clinical Scenario Consideration(s) Rationale/Comments
Characteristics
Pre-ART CD4 cell count <200 Do Not Use the Following Regimens: A higher rate of virologic failure has been observed in
Characteristics cells/mm3 • RPV-based regimens those with low pretreatment CD4 cell counts.
• DRV/r plus RAL
HIV RNA >100,000 Do Not Use the Following Regimens: Higher rates of virologic failure have been observed
copies/mL • RPV-based regimens in those with high pretreatment HIV RNA levels.
• ABC/3TC with EFV or ATV/r
• DRV/r plus RAL
HLA-B*5701 positive Do not use ABC-containing regimens. ABC hypersensitivity, a potentially fatal reaction,
or result unknown is highly associated with the presence of the HLA-
B*5701 allele.
ARV should be started Avoid NNRTI-based regimens. Transmitted mutations conferring NNRTI resistance
before HIV drug are more likely than mutations associated with PI or
resistance results Avoid ABC. INSTI resistance.
are available (e.g., in Recommended ART Regimens:
a person with acute HLA-B*5701 results may not be available rapidly.
• (DRV/r or DRV/c) plus tenofovira/FTC
HIV) or when rapid Transmitted resistance to DRV and DTG is rare, and
initiation of ART is •D TG plus tenofovira/FTC
these drugs have high barriers to resistance.
warranted
Refer to Table 6b for further guidance before initiating
DTG in persons of childbearing potential.
ART-Specific A 1-pill, once-daily STR Options as Initial ART Include: Do not use RPV-based regimens if HIV RNA is
Characteristics regimen is desired • BIC/TAF/FTC >100,000 copies/mL and CD4 cell count is <200/mm3.
• DOR/TDF/3TC Do not use DTG/ABC/3TC if patient is HLA-B*5701
• DRV/c/TAF/FTC positive.
• DTG/ABC/3TC Refer to Table 6b for further guidance before initiating
• EFV/TDF/FTC an INSTI in persons of childbearing potential.
• EFV/TDF/3TC See Appendix B, Table 8 for ARV dose
• EVG/c/TAF/FTC recommendations in the setting of renal impairment.
• EVG/c/TDF/FTC
• RPV/TAF/FTC
• RPV/TDF/FTC
Food effects Regimens that Can be Taken Without Oral bioavailability of these regimens is not
Regard to Food: significantly affected by food.
• BIC-, DOR-, DTG-, or RAL-based Refer to Table 6b for further guidance before initiating
regimens an INSTI in persons of childbearing potential.

Table 7. Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical
Scenarios (page 2 of 4)
Patient or
Characteristics
ART-Specific Food effects, Regimens that Should be Taken with Food: Food improves absorption of these regimens. RPV-
Characteristics, continued •A TV/r- or ATV/c-based regimens containing regimens should be taken with at least 390
continued calories of food.
• DRV/r- or DRV/c-based regimens
• EVG/c/TAF/FTCa
• EVG/c/TDF/FTCa
• RPV-based regimens
Regimens that Should be Taken on an Food increases EFV absorption and may increase
Empty Stomach: CNS side effects.
• EFV-based regimens
Presence Chronic kidney Avoid TDF unless the patient has TDF has been associated with proximal renal
of Other disease (defined as ESRD. Use ABC or TAF. tubulopathy. Higher rates of renal dysfunction have
Conditions CrCl <60 mL/min) been reported in patients using TDF in conjunction
ABC may be used if patient is HLA- with RTV-containing regimens.
B*5701 negative. If HIV RNA >100,000
copies/mL, do not use ABC/3TC plus An adjusted dose of TDF can be used in patients
(EFV or ATV/r). with ESRD or in those who are on hemodialysis.
Refer to Appendix B, Table 8 for specific dosing
TAF may be used if CrCl >30 mL/min. recommendations.
Consider avoiding ATV. TAF has less impact on renal function and lower rates
ART Options When ABC, TAF or TDF of proteinuria than TDF.
Cannot be Used: ATV has been associated with chronic kidney disease
• DTG plus 3TC in some observational studies.
• DRV/r plus 3TC
ABC has not been associated with renal dysfunction.
• DRV/r plus RAL (if CD4 cell count >200
cells/mm3 and HIV RNA <100,000 Refer to Table 6b for further guidance before initiating
copies/mL) an INSTI in persons of childbearing potential.
Liver disease with Some ARVs are contraindicated or may Refer to Appendix B, Table 8 for specific dosing
cirrhosis require dosage modification in patients recommendations.
with Child-Pugh class B or C disease.
Patients with cirrhosis should be carefully evaluated
by an expert in advanced liver disease.
Osteoporosis Avoid TDF. TDF is associated with decreases in BMD along
with renal tubulopathy, urine phosphate wasting, and
Use ABC or TAF.
resultant osteomalacia. TAF and ABC are associated
ABC may be used if patient is HLA- with smaller declines in BMD than TDF.
B*5701 negative. If HIV RNA >100,000
copies/mL, do not use ABC/3TC plus
(EFV or ATV/r).
Psychiatric illnesses Consider avoiding EFV- and RPV- EFV and RPV can exacerbate psychiatric symptoms
based regimens. and may be associated with suicidality.
Patients on INSTI-based regimens who INSTIs have been associated with adverse
have pre-existing psychiatric conditions neuropsychiatric effects in some retrospective cohort
should be closely monitored. studies and case series.
Some ARVs are contraindicated and See the drug-drug interaction tables (Tables 19a,
some psychiatric medications need dose 19b, and 19d) for dosing recommendations when
adjustments when coadministered with drugs used for psychiatric illnesses are used with
certain ARVs. certain ARVs.

Patient or
Characteristics
Presence HAD Avoid EFV-based regimens if EFV-related neuropsychiatric effects may confound
of Other possible. assessment of ART’s beneficial effects on
Conditions, improvement of HAD-related symptoms.
continued Favor DTG- or DRV-based regimens.
There is a theoretical CNS penetration advantage of
DTG- or DRV-based regimens.
Medication-assisted Opioid withdrawal may occur when EFV EFV reduces methadone concentrations and may
treatment for opioid is initiated in patients who are on a stable lead to withdrawal symptoms.
dependence dose of methadone.
See the drug-drug interaction tables (Tables 19a,
Clinical monitoring is recommended, 19b, and 19d) for dosing recommendations.
as medications used to treat opioid
dependence may need to be adjusted in
some patients.
High cardiac risk Consider avoiding ABC- and LPV/r An increased CV risk with ABC has been observed in
-based regimens. some studies.
If a boosted PI is the desired option, Observational cohort studies reported an association
an ATV-based regimen may have between some PIs (DRV, IDV, FPV, and LPV/r) and
advantages over a DRV-based regimen. an increased risk of CV events; this risk has not been
seen with ATV (see text). Further study is needed.
BIC-, DOR-, DTG-, RAL-, or RPV-based
regimens may be considered for those BIC-, DOR-, DTG-, RAL- or RPV-based regimens
with high cardiac risk. have more favorable lipid profiles than other
regimens, although evidence on whether this
improves CV outcomes is lacking.
an INSTI in persons of childbearing potential.
Cardiac QTc interval Consider avoiding EFV- or RPV-based High EFV or RPV concentrations may cause QT
prolongation regimens if patient is taking other prolongation.
medications with known risk of Torsades
de Pointes, or in patients at higher risk of
Torsades de Pointes.
Hyperlipidemia The Following ARV Drugs Have Been TDF has been associated with lower lipid levels than
Associated with Dyslipidemia: ABC or TAF.
• PI/r or PI/c Refer to Table 6b for further guidance before initiating
• EFV an INSTI in persons of childbearing potential.
• EVG/c
BIC, DOR, DTG, RAL, and RPV have
fewer lipid effects.
Patients with history Consider using regimens with a boosted These regimens have a high genetic barrier to
of poor adherence to PI or DTG. resistance.
non-ARV medications
or inconsistent BIC also has a high barrier to resistance, Refer to Table 6b for further guidance before initiating
engagement in care but there is currently no data on its an INSTI in persons of childbearing potential.
efficacy in this population.

Patient or
Characteristics
Presence Pregnancy Until more information is available, do not initiate a DTG-based regimen for those who are
of Other pregnant and within 12 weeks post-conception, because preliminary data suggest that there
Conditions, is an increased risk of NTDs in infants born to those who were receiving DTG at the time of
continued conception.6,7
Refer to Table 6b and the Perinatal Guidelines for further guidance on ARV use during
pregnancy.
Patients of Until more information is available, do not initiate a DTG-based regimen in these patients,
childbearing potential because preliminary data suggest that there is an increased risk of NTDs in infants born to those
who are planning to who were receiving DTG at the time of conception.6,7
become pregnant
or who are sexually Refer to Table 6b for further guidance before initiating an INSTI.
active and not using
effective contraception
Presence of HBV infection Use TDF or TAF, with FTC or 3TC, TDF, TAF, FTC, and 3TC are active against both HIV
Coinfections whenever possible. and HBV. 3TC- or FTC-associated HBV mutations
can emerge rapidly when these drugs are used
If TDF and TAF Are Contraindicated: without another drug that is active against HBV.
• For treatment of HBV, use FTC or 3TC
with entecavir and a suppressive ART
regimen (see HBV/HIV Coinfection).
HCV treatment Refer to recommendations in HCV/HIV Coinfection, with special attention to potential interactions
required between ARV drugs and HCV drugs.
Treating TB disease TAF and BIC are not recommended Rifamycins may significantly reduce TAF and BIC
with rifamycins with any rifamycin-containing exposures.
regimen.
Rifampin is a strong inducer of CYP3A4 and
If Rifampin is Used: UGT1A1 enzymes, causing significant decreases in
• The following are not recommended: concentrations of PIs, INSTIs, DOR, and RPV.
PI/c or PI/r, BIC, EVG, DOR, RPV, or Rifampin has a less significant effect on EFV
TAF. concentration than on the concentrations of other
• EFV can be used without dose NNRTIs, PIs, and INSTIs.
adjustment.
• If RAL is used, increase RAL dose to 800 an INSTI in persons of childbearing potential.
mg BID. Do not use once-daily RAL.
• Use DTG at 50 mg BID dose only See the drug-drug interaction tables (Tables 19a,
in patients without selected INSTI 19b, 19c, 19d and 19e) and TB/HIV Coinfection for
mutations (refer to product label). information on ARV use with rifamycins.
a
AF and TDF are two approved forms of tenofovir. TAF has fewer bone and kidney toxicities than TDF, whereas TDF is associated with lower
T
lipid levels. Safety, cost, and access are among the factors to consider when choosing between these drugs.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/
cobicistat; ATV/r = atazanavir/ritonavir; BIC= bictegravir; BID = twice daily; BMD = bone mineral density; COBI = cobicistat; CD4 = CD4 T
lymphocyte; CNS = central nervous system; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DOR = doravirine; DRV
= darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ESRD = end stage renal disease;
EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FPV = fosamprenavir; FTC = emtricitabine; HAD = HIV-associated dementia; HBV =
hepatitis B virus; HCV = hepatitis C virus; HLA = human leukocyte antigen; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LPV =
lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NTD = neural tube defect; PI = protease inhibitor;
PI/c = cobicistat-boosted protease inhibitor; PI/r = ritonavir-boosted protease inhibitor RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir;
STR = single-tablet regimen; TAF = tenofovir alafenamide; TB = tuberculosis; TDF = tenofovir disoproxil fumarate; UGT = uridine diphosphate
glucuronosyltransferase

Table 8a. Characteristics of Dual-Nucleoside Reverse Transcriptase Inhibitor Options Recommended
for Antiretroviral Therapy-Naive Patients
ABC/3TC TAF/FTC TDF/FTC TDF/3TC
Dosing Once daily Once daily Once daily Once daily
Frequency
Available • ABC/3TC • TAF 25 mg/FTC • TDF/FTC • TDF/3TC
Coformulations • D TG/ABC/3TC • BIC/TAF 25 mg/FTC • EFV/TDF/FTC • DOR/TDF/3TC
for ART-Naive
• DRV/c/TAF 10 mg/FTC • EVG/c/TDF/FTC • EFV 600 mg/TDF/3TC
Patients
• EVG/c/TAF 10 mg/FTC • RPV/TDF/FTC • EFV 400 mg/TDF/3TC
• RPV/TAF 25 mg/FTC
Adverse ABC: TAF: TDF: TDF:
Effects • HSR to ABC is associated • Renal insufficiency, • Renal insufficiency, • Renal insufficiency,
with the presence of HLA- proximal renal proximal renal proximal renal
B*5701 allele tubulopathy (less tubulopathy tubulopathy
• Increase in CV events is frequent than with TDF) • Decrease in BMD • Decrease in BMD
associated with ABC use • Decrease in BMD (less • Renal and bone toxicity • Renal and bone toxicity
in some, but not all, cohort than with TDF; similar are exacerbated by are exacerbated by
studies to ABC) pharmacologic boosters pharmacologic boosters
3TC: No significant
FTC: Nail pigmentation
adverse effects
Other •P erform HLA-B*5701 testing Also used for HBV treatment. Discontinuation may precipitate flair of HBV.
Considerations before initiating ABC; if result
is positive, do not start ABC See Appendix B, Table 8 for dose recommendations in patients with renal
and add ABC to allergy list insufficiency.
• If HIV RNA >100,000 copies/
mL, use only with DTG
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; BIC= bictegravir; BMD = bone mineral density;
CV = cardiovascular; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DTG = dolutegravir; EFV = efavirenz; EVG
= elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HBV = hepatitis B virus; HLA = human leukocyte antigen; HSR =
hypersensitivity reaction; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RPV = rilpivirine; STR = single-tablet
regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Table 8b. Characteristics of Integrase Strand Transfer Inhibitors That Are Recommended for
Antiretroviral Therapy-Naive Patients
Note: Preliminary data suggest that there may be an increased risk of NTDs in infants born to those who
were receiving DTG at the time of conception.6,7 Until more information is available:
• Pregnancy testing should be performed for those of childbearing potential prior to initiation of ART.
• DTG is not recommended for ART-naive individuals:
• Who are pregnant and within 12 weeks post-conception, or
• Who are of childbearing potential and who are planning to become pregnant or who are sexually active
and not using effective contraception.
Clinicians should refer to Table 6b for further guidance before initiating an INSTI.
BIC DTG EVG RAL
Dosing Frequency Once daily Once Daily: Once daily; requires • 400 mg BID, or
• In ART-naive or INSTI-naive boosting with COBI • 1200 mg (two 600-mg
persons tablets) once daily
Twice Daily:
• If used with certain CYP3A4
and UGT1A1 inducers; or
• In INSTI-experienced persons
with certain INSTI DRMs
STR Available for ART- BIC/TAF/FTC DTG/ABC/3TC • EVG/c/TAF/FTC No
Naive Patients • EVG/c/TDF/FTC
Available as a Single-Drug No Yes No Yes
Tablet
Approved for ART- No Yes, with BID dosing for No Yes, for patients with
Experienced Patients patients with some INSTI DRM to PI/r or NNRTIs,
DRMs but no DRM to INSTIs
Virologic Efficacy Against In vitro data indicate Yes, for some isolates; effective No No
EVG- or RAL-Resistant HIV activity, but no clinical with 50 mg BID dose
trial data are available
Adverse Effects Nausea, diarrhea (GI disturbance greater with EVG/c), headache, insomnia. Depression and suicidality are rare,
occurring primarily in patients with pre-existing psychiatric conditions.
↑ CPK (4%) Hypersensitivity, hepatotoxicity, ↑ TG, ↑ LDL ↑ CPK, myopathy,
↑ CPK, myositis hypersensitivity, SJS/TEN
CYP3A4 Drug-Drug CYP3A4 substrate CYP3A4 substrate (minor) EVG is a CYP3A4 substrate; No
Interactions COBI is a CYP3A4 inhibitor
Chelation with Poly-
Oral absorption of all INSTIs may be reduced by polyvalent cations. See Table 19d for recommendations regarding
valent Cation Supplements
dosing separation of INSTIs and these drugs.
and Antacids
Other Key Potential Drug UGT1A1 substrate, p-gp substrate, UGT1A1 EVG is a UGT1A1 substrate; UGT1A1 substrate
Interactions OCT2 and MATE1 substrate COBI is a p-gp inhibitor
inhibitor
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; BIC = bictegravir; BID = twice daily; COBI = cobicistat; CPK
= creatine phosphokinase; CYP = cytochrome P; DRM = drug resistance mutation; DTG = dolutegravir; EVG = elvitegravir; EVG/c = elvitegravir/
cobicistat; FTC = emtricitabine; GI = gastrointestinal; INSTI = integrase strand transfer inhibitor; LDL = low density lipoprotein; MATE = multidrug and
toxic compound extrusion; NNRTI = non-nucleoside reverse transcriptase inhibitor; NTD = neural tube defect; OAT = organic anionic transporter;
p-gp = p-glycoprotein; PI = protease inhibitor; PI/r = ritonavir-boosted protease inhibitor; RAL = raltegravir; SJS/TEN = Stevens Johnson Syndrome/
toxic epidermal necrolysis; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TG = triglyceride; UGT =
uridine diphosphate glucuronosyltransferase

Table 8c. Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors that are Recommended
for Antiretroviral Therapy-Naive Patients
DOR EFV RPV
Dosing Frequency Once daily Once daily Once daily
Food Requirement With or without food On an empty stomach With a meal
STR Available for ART- • DOR/TDF/3TC • EFV 600 mg/TDF/FTC • RPV/TAF/FTC
Naive Patients • EFV 600 mg/TDF/3TC • RPV/TDF/FTC
• EFV 400 mg/TDF/3TC
Available as a Single-Drug Yes Yes Yes
Tablet
Adverse Effects Generally well • CNS side effects, including dizziness, • Depression, headache
tolerated abnormal dreams, headache, •S kin rash
depression, suicidality, somnolence, and
insomnia • QT prolongation
• Skin rash
CYP3A4 Drug-Drug CYP3A4 substrate CYP3A4 substrate, mixed inducer/ CYP3A4 substrate
Interactions inhibitor
Other Significant Drug None CYP2B6 and 2C19 inducer RPV oral absorption is reduced with
Interactions increased gastric pH. Use of RPV
with PPIs is not recommended; see
Drug-Drug Interactions for dosing
recommendations when RPV is
coadministered with H2 blocker or
antacids.
Key to Acronyms: 3TC = lamivudine; CNS = central nervous system; CYP = cytochrome P; DOR = doravirine; EFV = efavirenz; FTC =
emtricitabine; H2 = histamine 2; PPI = proton pump inhibitor; RPV = rilpivirine; STR = single-tablet regimen; TAF = tenofovir alafenamide;
TDF = tenofovir disoproxil fumarate

Table 8d. Characteristics of Protease Inhibitor Options that are Recommended for Antiretroviral
Therapy-Naive Patients
ATV DRV
Dosing Frequency Once daily • Once daily for PI-naive patients
• Twice daily for PI-experienced patients with certain PI
mutations
PK Boosting PK-boosting with RTV or COBI is generally DRV should only be used with a PK booster (i.e., RTV or
recommended. Unboosted ATV is also FDA- COBI).
approved for ART-naive patients.
Fixed-Dose Formulation • ATV/c • DRV/c
• DRV/c/TAF/FTC
Available as a Single- Yes Yes
Drug Tablet
Adverse Effects • Jaundice • Skin rash
• Indirect hyperbilirubinemia • Increase in serum transaminases
• Cholelithiasis • Hyperlipidemia
• Nephrolithiasis • A higher cardiovascular risk was reported in participants
• PR prolongation taking DRV-based regimens than in those taking ATV-
based regimens in an observational cohort study.
CYP3A4 Drug-Drug CYP3A4 substrate, inhibitor CYP34A substrate, inhibitor
Interactions
Other Significant Drug ATV absorption is reduced when ATV is given N/A
Interactions with acid-lowering therapies. See Table 19a for
ATV dosing recommendations when the drug is
coadministered with acid-lowering agents.
Key to Acronyms: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; COBI = cobicistat; CYP = cytochrome P;
DRV = darunavir; DRV/c = darunavir/cobicistat; FDA = Food and Drug Administration; FTC = emtricitabine; PI = protease inhibitor; PK =
pharmacokinetic; RTV = ritonavir; TAF = tenofovir alafenamide

Table 9. Advantages and Disadvantages of Antiretroviral Components Recommended as Initial
Antiretroviral Therapy (page 1 of 5)
Note: All drugs within an ARV class are listed in alphabetical order.
ARV Class ARV Agent(s) Advantage(s) Disadvantage(s)
Dual-NRTI ABC/3TC • Coformulated with DTG • May cause life-threatening HSRs in patients who test
• Generic formulations are available for positive for the HLA-B*5701 allele. As a result, HLA-
ABC/3TC, ABC, and 3TC. B*5701 testing is required before use.
• In the ACTG 5202 study, patients with baseline HIV RNA
≥100,000 copies/mL showed inferior virologic responses
when ABC/3TC was given with EFV or ATV/r as opposed
to TDF/FTC. This difference was not seen when ABC/3TC
was used in combination with DTG.
• ABC use has been associated with CV disease and
cardiac events in some, but not all, observational studies.
TAF/FTC • Coformulated with BIC, DRV/c, EVG/c, or RPV • TDF is associated with lower lipid levels than TAF,
• Active against HBV; a recommended dual- perhaps because TDF results in higher plasma levels of
NRTI option for patients with HIV/HBV tenofovir, which lowers lipids.
coinfection
• Smaller decline in renal function, less
proteinuria, and smaller reductions in BMD
than TDF/FTC
• Approved for patients with eGFR ≥30 mL/min
TDF/3TC • Coformulated with DOR and EFV • Renal toxicity, including proximal tubulopathy and acute or
• Available as the following generic formulations: chronic renal insufficiency, especially when combined with
pharmacologic boosters.
• TDF
• 3TC • Osteomalacia has been reported as a consequence of
proximal tubulopathy.
• TDF/3TC
• Decreased BMD has been associated with use of TDF,
• EFV/TDF/3TC
especially when combined with pharmacologic boosters.
• Long-term clinical experience
• Active against HBV
TDF/FTC • Coformulated with EFV, EVG/c, and RPV as • Renal toxicity, including proximal tubulopathy and acute or
STRs chronic renal insufficiency, especially when combined with
• Active against HBV; a recommended dual- pharmacologic boosters.
NRTI option for patients with HIV/HBV • Osteomalacia has been reported as a consequence of
coinfection proximal tubulopathy.
• Better virologic responses than ABC/3TC in • Decreased BMD has been associated with use of TDF,
patients with baseline viral loads ≥100,000 especially when combined with pharmacologic boosters.
copies/mL when combined with ATV/r or EFV
• Associated with lower lipid levels than ABC or
TAF

INSTI BIC • Coformulated with TAF/FTC • Compared to other INSTIs, BIC has the shortest post-
• In trials in ART-naive participants, BIC marketing experience.
resistance was not detected • Oral absorption of BIC can be reduced by simultaneous
• No food requirement administration with drugs or supplements containing
polyvalent cations (e.g., Al-, Ca-, or Mg-containing antacids
or supplements, or multivitamin tablets with minerals). See
dosing recommendations in Table 19d.
• Inhibits tubular secretion of creatinine without affecting
glomerular function.
• CYP3A4 and UGT1A1 substrate (but not a CYP3A4
inducer or inhibitor); potential for drug interactions.
DTG • Higher barrier to resistance than EVG or RAL • Preliminary data suggests that DTG use before pregnancy
• Coformulated with ABC and 3TC and through conception may be associated with an
increased risk of NTDs in the infant. See text and Table 6b
• No food requirement for recommendations.
• No CYP3A4 interactions • Oral absorption of DTG can be reduced by simultaneous
• Favorable lipid profile administration with drugs containing polyvalent cations
(e.g., Al-, Ca-, or Mg-containing antacids or supplements,
or multivitamin tablets with minerals). See dosing
recommendations in Table 19d.
• Inhibits renal tubular secretion of Cr and can increase
serum Cr without affecting glomerular function.
• UGT1A1 substrate; potential for drug interactions (see
Table 19d).
• Depression and suicidal ideation (rare; usually in patients
with pre-existing psychiatric conditions).
EVG/c • Coformulated with TDF/FTC or TAF/FTC • EVG/c/TDF/FTC is only recommended for patients
• Compared with ATV/r, causes smaller with baseline CrCl ≥70 mL/min; this regimen should be
increases in total and LDL cholesterol discontinued if CrCl decreases to <50 mL/min.
• COBI is a potent CYP3A4 inhibitor, which can result in
significant interactions with CYP3A substrates.
• Oral absorption of EVG can be reduced by simultaneous
administration with drugs containing polyvalent cations
• COBI inhibits active tubular secretion of Cr and can
increase serum Cr without affecting renal glomerular
function.
• Has a lower barrier to resistance than boosted PI-, BIC-,
or DTG-based regimens.
• Food requirement.

INSTI, RAL • Compared to other INSTIs, has longest post- • Has a lower barrier to resistance than boosted PI-, BIC-,
continued marketing experience or DTG-based regimens.
• No food requirement • Increases in creatine kinase, myopathy, and
• No CYP3A4 interactions rhabdomyolysis have been reported.
• Favorable lipid profile • Rare cases of severe HSRs (including SJS and TEN)
have been reported.
• Higher pill burden than other INSTI-based regimens.
• No STR formulation.
• Oral absorption of RAL can be reduced by simultaneous
administration with drugs containing polyvalent cations
• UGT1A1 substrate; potential for drug interactions (see
Table 19d).
NNRTI DOR • Coformulated with TDF/3TC • Shorter-term clinical experience than with EFV and RPV.
• Compared to EFV, CNS side effects are less • Potential for CYP450 drug interactions (see Tables 19b,
frequent 20a and 20b).
• No food requirement • Treatment-emergent DOR resistance mutations may
• Favorable lipid profile confer resistance to certain NNRTIs.
EFV • EFV 600 mg is coformulated with TDF/FTC • Short-and long-term neuropsychiatric (CNS) side effects,
and TDF/3TC including depression and, in some studies, suicidality
• EFV 400 mg is coformulated with TDF/3TC and catatonia. Screening for depression and suicidality
is recommended in people with HIV who are taking a
• EFV 600-mg dose has long-term clinical regimen that includes EFV.
experience and EFV-based regimens (except
for EFV plus ABC/3TC) have well-documented • Teratogenic in nonhuman primates, although no rate
efficacy in patients with high HIV RNA increase has been seen in humans.
• Dyslipidemia
• Rash
• QTc interval prolongation; consider using an alternative
to EFV in patients taking medications with known risk of
causing Torsades de Pointes or in those at higher risk of
Torsades de Pointes.
• Transmitted resistance is more common than with PIs and
INSTIs.
• Greater risk of resistance at the time of treatment failure
than with PIs.
• Potential for CYP450 drug interactions (see Tables 19b
and 20a).
• Should be taken on an empty stomach (food increases
drug absorption and CNS toxicities).

NNRTI, RPV • Coformulated with TDF/FTC and TAF/FTC • Not recommended in patients with pre-ART HIV RNA
continued •R PV/TDF/FTC and RPV/TAF/FTC have >100,000 copies/mL or CD4 cell counts <200 cells/mm3
smaller pill sizes than other coformulated ARV because of higher rate of virologic failure in these patients.
drugs • Depression and suicidality
• Compared with EFV: • QTc interval prolongation; consider using an alternative
• Fewer CNS adverse effects to RPV in patients taking medications with known risk of
causing Torsades de Pointes or in those at higher risk of
• Fewer lipid effects Torsades de Pointes.
•F ewer rashes • Rash
• Transmitted resistance is more common than with PIs and
INSTIs.
• More NNRTI-, TDF-, and 3TC-associated mutations at
virologic failure than with regimens that contain EFV and
2 NRTIs.
• Potential for CYP450 drug interactions (see Tables 19b
and 20a).
• Meal requirement (>390 kcal)
• Requires acid for adequate absorption.
• Contraindicated with PPIs.
• Use with H2 antagonists or antacids with caution (see
Table 19a for detailed dosing information).
PIs ATV/c • Higher barrier to resistance than NNRTIs, • Commonly causes indirect hyperbilirubinemia, which may
or EVG, and RAL manifest as scleral icterus or jaundice.
ATV/r • PI resistance at the time of treatment failure is • Food requirement
uncommon with PK-enhanced PIs • Absorption depends on food and low gastric pH (see
• ATV/c and ATV/r have similar virologic activity Table 19a for interactions with H2 antagonists, antacids,
and toxicity profiles and PPIs).
• Observational cohort studies have found an • Nephrolithiasis, cholelithiasis, nephrotoxicity
association between some PIs (DRV, LPV/r, • GI adverse effects
FPV, IDV) and an increased risk of CV events;
this risk has not been seen with ATV. Further • CYP3A4 inhibitors and substrates: potential for drug
study is needed. See text for discussion. interactions (see Table 19a).
• Individual ATV and RTV components available
as generics
ATV/c • Coformulated tablet • COBI inhibits active tubular secretion of Cr and can
increase serum Cr without affecting renal glomerular
(Specific function.
considerations)
• Coadministration with TDF is not recommended in
patients with CrCl <70 mL/min.
• COBI (like RTV) is a potent CYP3A4 inhibitor, which can
result in significant interactions with CYP3A substrates.
DRV/c • Higher barrier to resistance than NNRTIs, • Skin rash
or EVG, and RAL • Food requirement
DRV/r • PI resistance at the time of treatment failure is • GI adverse effects
uncommon with PK-enhanced PIs
• CYP3A4 inhibitors and substrates: potential for drug
interactions (see Table 19a).
• Increased CV risk reported in one observational cohort
study.

PIs, DRV/c • Coformulated as DRV/c and DRV/c/TAF/FTC • COBI inhibits active tubular secretion of Cr and can
continued increase serum Cr without affecting renal glomerular
(Specific function.
considerations)
• Coadministration with TDF is not recommended in
patients with CrCl <70 mL/min.
• COBI (like RTV) is a potent CYP3A4 inhibitor, which can
result in significant interactions with CYP3A substrates.
LPV/r • Only RTV-coformulated PI • Requires RTV 200 mg per day.
• No food requirement • Possible higher risk of MI associated with cumulative use
of LPV/r.
• PR and QT interval prolongation have been reported.
Use with caution in patients at risk of cardiac conduction
abnormalities or in patients receiving other drugs with
similar effects.
• Possible nephrotoxicity
• CYP3A4 inhibitors and substrates: potential for drug
interactions (see Table 19a).
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c
= atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC= bictegravir; BMD = bone mineral density; Ca = calcium; CD4 = CD4 T lymphocyte;
CNS = central nervous system; COBI = cobicistat; Cr = creatinine; CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DOR
= doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; eGFR = estimated glomerular
filtration rate; EFV = efavirenz; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FDC = fixed=dose combination; FPV = fosamprenavir; FTC =
emtricitabine; GI = gastrointestinal; HBV = hepatitis B virus; HLA = human leukocyte antigen; HSR = hypersensitivity reaction; IDV = indinavir;
INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LPV = lopinavir; LPV/r = lopinavir/ritonavir; Mg = magnesium; MI =
myocardial infarction; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NTD = neural
tube defect; PI = protease inhibitor; PK = pharmacokinetic; PPI = proton pump inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir;
SJS = Stevens-Johnson syndrome; STR = single-tablet regimen; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TEN = toxic
epidermal necrosis; UGT = uridine diphosphate glucuronosyltransferase

Table 10. Antiretroviral Components or Regimens Not Recommended as Initial Therapy (page 1 of 3)
ARV Components or Regimens Reasons for Not Recommending as Initial Therapy
NRTIs
ABC/3TC/ZDV (Coformulated) • Inferior virologic efficacy
As triple-NRTI combination regimen
ABC/3TC/ZDV plus TDF • Inferior virologic efficacy
As quadruple-NRTI combination regimen
d4T plus 3TC • Significant toxicities (including lipoatrophy, peripheral neuropathy) and hyperlactatemia
(including symptomatic and life-threatening lactic acidosis, hepatic steatosis, and
pancreatitis)
ddI plus 3TC (or FTC) • Inferior virologic efficacy
• Limited clinical trial experience in ART-naive patients
• ddI toxicities, such as pancreatitis and peripheral neuropathy
ddI plus TDF • High rate of early virologic failure
• Rapid selection of resistance mutations
• Potential for immunologic nonresponse/CD4 cell decline
• Increased ddI drug exposure and toxicities

NRTIs, continued
ZDV/3TC • Greater toxicities (including bone marrow suppression, GI toxicities, skeletal muscle
myopathy, cardiomyopathy, and mitochondrial toxicities such as lipoatrophy, lactic
acidosis, and hepatic steatosis) than recommended NRTIs
NNRTIs
DLV • Inferior virologic efficacy
• Inconvenient (three times daily) dosing
ETR • Insufficient data in ART-naive patients
NVP • Associated with serious and potentially fatal toxicity (hepatic events and severe rash,
including SJS and TEN)
• When compared to EFV, NVP did not meet noninferiority criteria
PIs
ATV (Unboosted) • Less potent than boosted ATV
DRV (Unboosted) • Use without RTV or COBI has not been studied
FPV (Unboosted) • Virologic failure with unboosted FPV-based regimen may result in selection of mutations
or that confer resistance to FPV and DRV
FPV/r • Less clinical trial data for FPV/r than for other RTV-boosted PIs
IDV (Unboosted) • Inconvenient dosing (3 times daily with meal restrictions)
•F
luid requirement
• IDV toxicities, such as nephrolithiasis and crystalluria
IDV/r • Fluid requirement
• IDV toxicities, such as nephrolithiasis and crystalluria
LPV/r • Higher pill burden than other PI-based regimens
• Higher RTV dose than other PI-based regimens
• GI intolerance
NFV • Inferior virologic efficacy
• Diarrhea
RTV as sole PI • High pill burden
• GI intolerance
• Metabolic toxicity
SQV (Unboosted) • Inadequate bioavailability
• Inferior virologic efficacy
SQV/r • High pill burden
• Can cause QT and PR prolongation; requires pretreatment and follow-up ECG
TPV/r • Inferior virologic efficacy
• Higher rate of adverse events than other RTV-boosted PIs
• Higher dose of RTV required for boosting than other RTV-boosted PIs
Entry Inhibitors
T-20 • Only studied in patients with virologic failure
Fusion Inhibitor • Twice-daily subcutaneous injections
• High rate of injection site reactions
IBA • Only studied in a very small number of patients with virologic failure
CD4 Post-Attachment Inhibitor • Requires IV therapy
• High cost

Entry Inhibitors, continued
MVC • Requires testing for CCR5 tropism before initiation of therapy
CCR5 Antagonist • No virologic benefit when compared with other recommended regimens
• Requires twice-daily dosing
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; CD4 = CD4
T lymphocyte; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DLV = delavirdine; DRV = darunavir; ECG = electrocardiogram; EFV
= efavirenz; ETR = etravirine; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; GI = gastrointestinal; IBA =
ibalizumab; IDV = indinavir; IDV/r = indinavir/ritonavir; IV = intravenous; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV
= nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine;
PI = protease inhibitor; RTV = ritonavir; SJS = Stevens Johnson Syndrome; SQV = saquinavir; SQV/r = saquinavir/ritonavir; T-20 =
enfuvirtide; TDF = tenofovir disoproxil fumarate; TEN = toxic epidermal necrolysis; TPV = tipranavir; TPV/r = tipranavir/ritonavir; ZDV =
zidovudine

Table 11. Antiretroviral Options for Patients with Virologic Failure
Designing a new regimen for patients with treatment failure should always be guided by ARV history and
results from current and past resistance testing. This table summarizes the text above and displays the most
common or likely clinical scenarios seen in patients with virologic failure. For more detailed descriptions,
please refer to the text above and/or consult an expert in drug resistance to assist in the design of a new
regimen. It is also crucial to provide continuous adherence support to all patients before and after regimen
changes.
Preliminary data from Botswana suggested that there is an increased risk of NTDs in infants born to
individuals who were receiving DTG at the time of conception.47,48 Pregnancy testing should therefore be
performed for those of childbearing potential prior to initiation of DTG. If there is an alternative option,
DTG should not be prescribed for those who are pregnant and within 12 weeks post-conception or those
who are of childbearing potential and who are planning to become pregnant or who are not using effective
contraception. When DTG is the only treatment option, or one of few treatment options, providers should
counsel individuals who are pregnant or of childbearing potential about the possible association between
NTDs and DTG use during conception. The decision of whether to initiate or continue DTG should be made
after careful consideration of this risk and the risks of persistent viremia in the patient and HIV transmission
to the fetus if pregnancy occurs while the patient is not on effective ART.
Type of
Clinical
Failing Resistance Considerations New Regimen Optionsa,b Goal
Scenario
Regimen
First Regimen NNRTI plus Most likely resistant to NNRTI +/- • Boosted PI plus 2 NRTIs (at least 1 active) Resuppression
Failure 2 NRTIs 3TC/FTC (i.e., NNRTI mutations (AIII); or
+/- M184V/I).c Additional NRTI • DTGd plus 2 NRTIs (at least 1 active) (AI); or
mutations may also be present.
• Boosted PI plus INSTI (AIII)
Boosted Most likely no resistance, or • Continue same regimen (AII); or Resuppression
PI plus 2 resistance only to 3TC/FTC (i.e., • Another boosted PI plus 2 NRTIs (at least 1
NRTIs M184V/I, without resistance to active) (AII); or
other NRTIs)c
• INSTI plus 2 NRTIs (at least 1 active; if only
1 of the NRTIs is fully active, or, if adherence
is a concern, DTGd is preferred over the other
INSTIs) (AIII); or
• Another boosted PI plus INSTI (BIII)
INSTI plus No INSTI resistance (can • Boosted PI plus 2 NRTIs (at least 1 active) Resuppression
2 NRTIs have 3TC/FTC resistance, i.e., (AIII); or
only M184V/I, usually without • DTGd plus 2 NRTIs (at least 1 active) (AIII); or
resistance to other NRTIs)c
• Boosted PI plus INSTI (BIII)

Table 11. Antiretroviral Options for Patients with Virologic Failure
Type of
Clinical
Failing Resistance Considerations New Regimen Optionsa,b Goal
Scenario
Regimen
First Regimen INSTI plus EVG or RAL +/- 3TC/FTC • Boosted PI plus 2 NRTIs (at least 1 active) Resuppression
Failure, 2 NRTIs resistance (AIII); or
continued • DTGd,e twice daily (if patient is sensitive to
Resistance to first-line BIC or
DTG is rare DTG) plus 2 active NRTIs (AIII); or
• DTGd,e twice daily (if patient is sensitive to
DTG) plus a boosted PI (AIII)
• BIC has not been studied in this setting and
cannot be recommended.
Second Drug Use past and current genotypic • At least 2, and preferably 3, fully active agents Resuppression
Regimen Failure resistance +/- phenotypic resistance testing (AI)
and Beyond with active and ART history in designing new • Partially active drugs may be used when no
treatment regimen other options are available
options
• Consider using an ARV with a different
mechanism of action
Multiple or Use past and current genotypic • Identify as many active or partially active drugsResuppression,
extensive and phenotypic resistance testing as possible based on resistance test results if possible;
drug to guide therapy • Consider using an ARV with a different otherwise,
resistance mechanism of action keeping viral
with few Consider viral tropism assay if load as low as
treatment use of MVC is considered • Consider enrollment into clinical trials or possible and
options expanded access programs for investigational CD4 cell count
Consult an expert in drug agents, if available
resistance, if needed as high as
• Discontinuation of ARVs is not recommended. possible
Previously Unknown Obtain medical records if possible • Consider restarting the old regimen, and obtain Resuppression
on Treatment, viral load and resistance testing 2–4 weeks
Suspected Drug Resistance testing may be helpful after reintroduction of therapy
Resistance, in identifying drug resistance
Limited or mutations, even if the patient has • If there is no available ARV history, consider
been off ART. Keep in mind that initiating a regimen with drugs with high
Incomplete ART genetic barriers to resistance (e.g., DTGd,e and/
and Resistance resistance mutations may not be
detected in the absence of drug or boosted DRV)
History
pressure.
a
There are insufficient data to provide a recommendation for the continuation of 3TC/FTC in the presence of M184V/I.
b
hen switching an ARV regimen in a patient with HIV/HBV coinfection, ARV drugs that are active against HBV should be continued as
W
part of the new regimen. Discontinuation of these drugs may lead to the reactivation of HBV, which may result in serious hepatocellular
damage.
c
If other NRTI resistance mutations are present, use resistance test results to guide NRTI usage in the new regimen.
d
reliminary data from Botswana suggested that there is an increased risk of NTDs in infants born to those who were receiving DTG at
P
the time of conception.47,48 Pregnancy testing should therefore be performed for those of childbearing potential prior to initiation of DTG.
Please refer to the discussion at the beginning of this table for further recommendations.
e
Response to DTG depends on the type and number of INSTI mutations.
Key to Acronyms: 3TC = lamivudine; ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; CD4 = CD4 T lymphocyte;
DRV = darunavir; DTG = dolutegravir; EVG = elvitegravir; FTC = emtricitabine; HBV = hepatitis B virus; INSTI = integrase strand transfer
inhibitor; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor;
NTD = neural tube defect; PI = protease inhibitor; RAL = raltegravir

Table 12. Identifying, Diagnosing, and Treating Acute and Recent HIV-1 Infection
Suspicion of Acute HIV-1 Infection:

• Health care providers should consider the possibility of acute HIV-1 infection in individuals with signs, symptoms, or the laboratory
findings described below and recent (within 2 to 6 weeks) high risk of exposure to HIV-1.a
• Signs, symptoms, or laboratory findings of acute HIV-1 infection may include but are not limited to one or more of the following:
fever, lymphadenopathy, skin rash, myalgia, arthralgia, headache, diarrhea, oral ulcers, leucopenia, thrombocytopenia, and
transaminase elevation.
• H
igh-risk exposures include sexual contact with a person who has HIV-1 infection or a person at risk of HIV-1 infection, sharing
of injection drug use paraphernalia, or any exposure in which an individual’s mucous membranes or breaks in the skin come in
contact with bodily fluid that potentially carries HIV-1.
• Differential Diagnosis: The differential diagnosis of HIV-1 infection may include but is not limited to viral illnesses such as EBV and
non-EBV (e.g., cytomegalovirus) infectious mononucleosis syndromes, influenza, viral hepatitis, streptococcal infection, or syphilis.
Evaluation/Diagnosis of Acute HIV-1 Infection:
• Acute HIV-1 infection is defined as detectable HIV-1 RNA or p24 antigen (the antigen used in currently available HIV Ag/Ab combination
assays) in the setting of a negative or indeterminate HIV-1 antibody test result.
• A reactive HIV antibody test result or Ag/Ab combination test result must be followed by supplemental confirmatory testing.
• A negative or indeterminate HIV-1 antibody test result in a person with a reactive Ag/Ab test result or in whom acute HIV-1 infection is
suspected requires plasma HIV-1 RNA testing to diagnose acute HIV-1 infection.
• A positive result on a quantitative or qualitative plasma HIV-1 RNA test in the setting of a negative or indeterminate antibody test result
indicates that acute HIV-1 infection is highly likely. In this case, the diagnosis of HIV-1 infection should be later confirmed by subsequent
documentation of HIV-1 antibody seroconversion.
Antiretroviral Therapy After Diagnosis of Early HIV-1 Infection:
• ART is recommended for all individuals with HIV-1 (AI) and should be offered to all patients with early HIV-1 infection.
• A pregnancy test should be performed for all individuals who receive a diagnosis of early HIV infection and who are of childbearing
potential (AIII).
• Pregnant patients with early HIV-1 infection should begin ART as soon as possible for their own health and to prevent perinatal
transmission of HIV-1 (AI).
• A blood sample for genotypic drug resistance testing should be obtained before initiation of ART to guide the selection of the regimen
(AII), but ART should be initiated as soon as possible, often prior to availability of resistance test results. If resistance is subsequently
identified, treatment should be modified appropriately.
• If no resistance data are available, then a pharmacologically boosted PI-based regimen is recommended, because resistance to PIs
emerges slowly and clinically significant transmitted resistance to PIs is uncommon. Boosted DRV (DRV/r or DRV/c) plus FTC and either
TDF or TAF is a recommended regimen in this setting (AIII). For similar reasons, DTG plus FTC and either TDF or TAF are reasonable
options, although the data regarding transmission of INSTI-resistant HIV and the efficacy of this regimen in early HIV infection are
limited (AIII).
• Preliminary data from Botswana suggested that infants born to women who were receiving DTG at the time of conception have an
increased risk of neural tube defects. Until more information is available, DTG should not be prescribed for individuals:
ho are pregnant and within 12 weeks post-conception (AII);
•W
ho are of childbearing potential, who are sexually active, and who are not using effective contraception (AII); or
•W
• Who are contemplating pregnancy (AII).
• In patients without transmitted drug-resistant virus, ART should be initiated with one of the combination regimens recommended for
patients with chronic HIV-1 infection (see What to Start) (AIII).
• Once initiated, the goal of ART should be sustained plasma virologic suppression, and ART should be continued indefinitely (AIII).
a
In some settings, behaviors that increase the risk of HIV-1 infection may not be recognized or perceived as risky by the health care
provider or the patient, or both. Thus, even in the absence of reported high-risk behaviors, symptoms and signs consistent with acute
retroviral syndrome should motivate practitioners to consider a diagnosis of acute HIV-1 infection.
Key to Acronyms: Ag/Ab = antigen/antibody; ART = antiretroviral therapy; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r =
darunavir/ritonavir; DTG = dolutegravir; EBV = Epstein-Barr virus; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; PI =
protease inhibitor; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate

Table 13. Concomitant Use of Selected Antiretroviral Drugs and Hepatitis C Virus Direct-Acting Antiviral Drugs for Treatment of HCV in
Adults with HIV (page 1 of 4)
The recommendations in this table for concomitant use of selected HIV drugs with FDA-approved HCV DAA drugs are based on available PK interaction
data or are predictions based on the known metabolic pathway of the agents. In some cases, there are not enough data to make any recommendations, and
these instances are indicated in the table. In all cases where HIV and HCV drugs are used concomitantly, patients should be closely monitored for HIV and
HCV virologic efficacy and potential toxicities. As the field of HCV therapy is rapidly evolving, readers should also refer to the latest drug product labels
and the HCV Guidance for updated information.
Note: Interactions with FPV, IDV, NFV, and SQV are not included in this table. Please refer to the FDA product labels for information regarding drug
interactions with these HIV PIs.
HCV Direct-Acting Antiviral Agents

Coformulated
SHOULD NOT BE USED IN THOSE WITH MODERATE TO SEVERE HEPATIC IMPAIRMENT
(Cirrhosis classified as Child-Pugh class B or C)
NS5A NS5B
Inhibitor Inhibitor NS5A/NS5B NS5A Inhibitor/ NS5A Inhibitor/ NS5A Inhibitor/
Selected NS5A/NS5B NS5A/NS5B Inhibitor/ NS3/4A NS3A/4A NS3A/4A Protease NS3A/4A
HIV Drugs Inhibitor Inhibitor NS3/4A Protease Protease Protease Inhibitor plus Protease Inhibitora
Inhibitor Inhibitor Inhibitor NS5B Inhibitor
Ombitasvir/
Sofosbuvir/
Ledipasvir/ Sofosbuvir/ Glecaprevir/ Elbasvir/ Paritaprevir/
Daclatasvir Sofosbuvir Velpatasvir/ Simeprevir
Sofosbuvir Velpatasvir Pibrentasvir Grazoprevir Ritonavir plus
Voxilaprevir
Dasabuvir a
NRTIs
3TC ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
ABC ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
FTC ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
TDF ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
Monitor for TDF Monitor for TDF Monitor for TDF
toxicity. toxicity. toxicity.
TAF ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
PIs
Unboosted ✓ ✓ ✓ ✓ ✘ ✘ ✘ ✓b ✘
ATV

Coformulated
NS5A NS5B
Ombitasvir/
Sofosbuvir/
Voxilaprevir
Dasabuvira
PIs, continued
ATV/r or ✓ ✓ ✘ ✘ ✘ ✓c ✘
ATV/c ↓ DCV dose
to 30 mg/day ✓ ✓
If a PI/r or PI/c If a PI/r or PI/c
DRV/r or ✓ ✓ ✓ ✘ ✘ ✘ ✘
is used with is used with
DRV/c If a PI/r is used
TDF, ↑ TDF TDF, ↑ TDF
with TDF, ↑ TDF
concentrations concentrations
concentrations.
are expected. If are expected. If
Monitor for
coadministration coadministration
TDF-associated
is necessary, is necessary,
toxicities.d
monitor for monitor for
Consider
TDF-associated TDF-associated
monitoring for
toxicities.d toxicities.d
hepatotoxicity.e
LPV/r ✓ ✓ ✘ ✘ ✘ ✘ ✘
TPV/r ? ✘ ✘ ✘ ✘ ✘ ✘ ✘ ✘
NNRTIs
DOR ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
EFV ✓ ✓ If used with TDF, ✘ ✘ ✘ ✘ ✘ ✘
↑ DCV dose monitor for TDF
to 90 mg/day toxicity.
ETR ✓ ✓ ✘ ✘ ✘ ✘ ✘ ✘
↑ DCV dose
to 90 mg/day

Coformulated
NS5A NS5B
Ombitasvir/
Sofosbuvir/
Voxilaprevir
Dasabuvira
NNRTIs, continued
NVP ✓ ✓ ✓ ✘ ✘ ✘ ✘ ✘ ✘
↑ DCV dose If used with TDF,
to 90 mg/day monitor for TDF
RPV ✓ ✓ toxicity. ✓ ✓ ✓ ✓ ✘ ✓
INSTIs
BIC/TAF/FTC ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
DTG ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
If used with TDF,
monitor for TDF
toxicity.
EVG/c/TDF/ ✓ ✓ ✘ ✓ ✓ ✓ ✘ ✘ ✘
FTC ↓ DCV dose If used with TDF, If used with TDF, If used with TDF,
to 30 mg/day monitor for TDF monitor for TDF monitor for TDF
toxicity. toxicity. Consider toxicity. Consider
monitoring for monitoring for
hepatotoxicity.e hepatotoxicity.f
EVG/c/TAF/ ✓ ✓ ✓ ✓ ✓ ✓ ✘ ✘ ✘
FTC ↓ DCV dose Consider Consider
to 30 mg/day monitoring for monitoring for
hepatotoxicity.e hepatotoxicity.f
RAL ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓
CCR5 Antagonist
MVC ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✘ ✓

a
Dasabuvir must be prescribed with ombitasvir/paritaprevir/RTV.
b
educe ATV dose to 300 mg and instruct the patient to take it in the morning at same time as ombitasvir/paritaprevir/RTV plus dasabuvir. If RTV cannot be used, choose an alternative
R
HCV regimen.
c
his HCV regimen contains RTV. If ATV is part of the ARV regimen, prescribe ATV 300 mg without COBI or RTV. It should be taken in the morning at the same time as ombitasvir/
T
paritaprevir/RTV plus dasabuvir. Resume RTV or COBI regimen when HCV therapy is completed.
d
Consider using an alternative HCV treatment or ARV regimen to avoid increases in TDF exposure. If co-administration is necessary, monitor patient for TDF-associated adverse reactions.
e
oxilaprevir exposures can increase when it is coadministered with pharmacologically boosted DRV or EVG. Until more safety data in clinical settings becomes available, patients who are
V
receiving voxilaprevir and pharmacologically boosted DRV or EVG should be monitored for hepatotoxicity.
f
lecaprevir exposures can increase when it is coadministered with EVG/c. Until more safety data in clinical settings becomes available, patients who are receiving glecaprevir and EVG/c
G
should be monitored for hepatotoxicity.
Key to Symbols:
✓ = ARV agents that can be used concomitantly
✘ = ARV agents not recommended
? = data limited or not available on pharmacokinetic interactions with ARV drug
↑ = increase
↓ = decrease
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; COBI =
cobicistat; DAA = direct-acting antiviral agents; DCV = daclatasvir; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; DSV
= dasabuvir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; FDA = Food and Drug Administration; EVG/c = elvitegravir/cobicistat; FPV = fosamprenavir; FTC = emtricitabine; HCV
= hepatitis C virus; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI
= nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; PK = pharmacokinetic; RAL =
raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV/r = tipranavir/ritonavir

Table 14. Strategies to Improve Linkage to Care, Retention in Care, Adherence to Appointments, and
Adherence to Antiretroviral Therapy (page 1 of 2)
Strategies Examples
Provide an accessible, trustworthy, • Care providers, nurses, social workers, case managers, pharmacists, and medication
nonjudgmental multidisciplinary health managers.
care team.
Strengthen early linkage to care and • Encourage health care team participation in linkage to and retention in care.
retention in care. • Use ARTAS training (if available).
Evaluate patient’s knowledge • Keeping the patient’s current knowledge base in mind, provide information about HIV,
about HIV infection, prevention, including the natural history of the disease, HIV viral load and CD4 count and expected
and treatment and, based on this clinical outcomes according to these parameters, therapeutic and prevention consequences
assessment, provide HIV-related of poor adherence, and importance of staying in HIV care.
information.
Identify facilitators, potential barriers to • Assess patient’s cognitive competence and impairment.
adherence, and necessary medication • A ssess behavioral and psychosocial challenges, including depression, mental illnesses,
management skills both before starting levels of social support, levels of alcohol consumption and current substance use,
ART and on an ongoing basis. nondisclosure of HIV serostatus, and stigma.
• Identify and address language and literacy barriers.
• Assess beliefs, perceptions, and expectations about taking ART (e.g., impact on health, side
effects, disclosure issues, consequences of poor adherence).
• Ask about medication-taking skills and foreseeable challenges with adherence (e.g., past
difficulty keeping appointments, adverse effects from previous medications, issues managing
other chronic medications, need for medication reminders and organizers).
• Assess structural issues, including unstable housing, lack of income, unpredictable daily
schedule, lack of prescription drug coverage, lack of continuous access to medications,
transportation problems.
Provide needed resources. • Provide or refer for mental health and/or substance abuse treatment.
• Provide resources to obtain prescription drug coverage (e.g., Common Patient Assistance
Program Application (CPAPA): http://bit.ly/CommonPAPForm; Pharmaceutical Company HIV
Patient Assistance Programs and Cost-Sharing Assistance Programs: http://bit.ly/1XIahvN
• Provide resources about stable housing, social support, transportation assistance, and
income and food security.
Involve the patient in ARV regimen • Review potential side effects, dosing frequency, pill burden, storage requirements, food
selection. requirements, and consequences of poor adherence.
• Assess daily activities and tailor regimen to predictable and routine daily events.
• Consider preferential use of PI/r-based or DTG-based ART if poor adherence is anticipated.
• Consider use of STR formulations.
• Assess if cost/copayment for drugs will affect adherence and access to medications.
Assess adherence at every clinic visit. • Monitor viral load as a strong biologic measure of adherence.
• Use a simple behavioral rating scale or self-reported assessment.
• Employ a structured format that normalizes or assumes less-than-perfect adherence and
minimizes socially desirable or “white-coat adherence” responses.
• Ensure that other members of the health care team also assess and support adherence.
Use positive reinforcement to foster • Inform patients of low or nondetectable levels of HIV viral load and increases in CD4 cell
adherence success. counts.
• Thank patients for attending their appointments.

Table 14. Strategies to Improve Linkage to Care, Retention in Care, Adherence to Appointments, and
Adherence to Antiretroviral Therapy (page 2 of 2)
Strategies Examples
Identify the type of and reasons for • Failure to understand dosing instructions.
poor adherence and target ways to • Complexity of regimen (e.g., pill burden, size, dosing schedule, food requirements,
improve adherence. polypharmacy).
• Pill aversion or pill fatigue.
• Adverse effects.
• Inadequate understanding of drug resistance and its relationship to adherence.
• Patient is unaware of appointments or appointments are not scheduled with proper patient
input.
• Cost-related issues (copays for medications or visits, missed work time).
• Depression, drug and alcohol use, homelessness, poverty.
• Stigma of taking pills or attending HIV-related appointments.
• Nondisclosure of status leading to missed doses, refills, or appointments.
Select from among available effective • See https://www.cdc.gov/hiv/research/interventionresearch/compendium/index.html for a
adherence and retention interventions. summary of best practice interventions to improve linkage, retention, and adherence.
• Use adherence-related tools to complement education and counseling interventions (e.g., text
messaging, pill box monitors, pill boxes, alarms).
• Use community resources to support adherence (e.g., visiting nurses, community workers,
family, peer advocates, transportation assistance).
• Use patient prescription assistance programs (see above, under “Provide needed
resources”).
• Use motivational interviews.
• Provide outreach for patients who drop out of care
• Use peer or paraprofessional treatment navigators.
• Recognize positive clinical outcomes resulting from better adherence.
• Arrange for DOT in persons in substance use treatment (if feasible).
• Enhance clinic support and structures to promote linkage and retention (reminder calls,
flexible scheduling, open access, active referrals, and improved patient satisfaction).
Systematically monitor retention in • Record and follow up on missed visits.
care.
Key to Acronyms: ART = antiretroviral therapy; ARTAS = Anti-Retroviral Treatment and Access to Services; ARV = antiretroviral; CD4 =
CD4 T lymphocyte; DOT = directly observed therapy; DTG = dolutegravir; PI/r = ritonavir-boosted protease inhibitor; STR = single tablet
regimen

Table 15. Common and/or Severe Adverse Effects Associated with Antiretroviral Therapy (page 1 of 5)
“N/A” indicates either that there are no reported cases for that particular side effect or that data for that specific ARV drug class are not available.
See Appendix B for additional information listed by drug.
Drug Class
Adverse Effect
NRTIs NNRTIs PIs INSTIs EIs
Bleeding Events N/A N/A Spontaneous bleeding, hematuria in N/A N/A
hemophilia
TPV: Intracranial hemorrhage
is associated with CNS lesions,
trauma, alcohol abuse, hypertension,
coagulopathy, anticoagulant or
antiplatelet agents, and the use of
vitamin E supplements.
Bone Density TDF: Associated with greater N/A
Effects loss of BMD than other NRTIs.
Osteomalacia may be associated
with renal tubulopathy and urine
phosphate wasting. Decreases in BMD observed after the initiation of any ART regimen.
TAF: Associated with smaller

declines in BMD than those seen
with TDF.
Bone Marrow ZDV: Anemia, neutropenia N/A N/A N/A N/A
Suppression
Cardiac N/A RPV, EFV: QTc prolongation SQV/r, ATV/r, and LPV/r: PR N/A N/A
Conduction prolongation. Risk factors include pre-
Effects existing heart disease and the use of
other medications.
SQV/r: QT prolongation. Obtain ECG
before administering SQV.
Cardiovascular ABC and ddI: Associated with N/A DRV, FPV, IDV, and LPV/r: Associated N/A N/A
Disease an increased risk of MI in with cardiovascular events in some
some cohort studies. Absolute cohorts
risk greatest in patients with
traditional CVD risk factors.
Cholelithiasis N/A N/A ATV: Cholelithiasis and kidney stones N/A N/A
may present concurrently. Median
onset is 42 months.
Drug Class
Adverse Effect
Diabetes Mellitus ZDV, d4T, and ddI N/A Reported for some (IDV, LPV/r), but not N/A N/A
and Insulin all, PIs.
Resistance
Dyslipidemia d4T > ZDV > ABC: ↑ TG and LDL EFV: ↑ TG, ↑ LDL, ↑ HDL All RTV- or COBI-Boosted PIs: ↑ TG, ↑ EVG/c: ↑ TG, ↑ LDL, ↑ HDL N/A
LDL, ↑ HDL
TAF: ↑ TG, ↑ LDL, ↑ HDL (no
change in TC:HDL ratio) LPV/r and FPV/r > DRV/r and ATV/r:
↑ TG
TDF has been associated with
lower lipid levels than ABC or
TAF.
Gastrointestinal ddI and ZDV > Other NRTIs: N/A GI intolerance (e.g., diarrhea, nausea, EVG/c: Nausea and IBA: 8% of
Effects Nausea and vomiting vomiting) diarrhea patients reported
diarrhea in a study
ddI: Pancreatitis NFV and LPV/r > DRV/r and ATV/r: of 40 people.
Diarrhea
Hepatic Effects Reported with most NRTIs. EFV: Most cases relate to an All PIs: Drug-induced hepatitis and N/A MVC:
increase in transaminases. hepatic decompensation have been Hepatotoxicity with
ZDV, d4T, and ddI: Steatosis Fulminant hepatitis leading to reported; greatest frequency occurs or without rash or
ddI: Prolonged exposure linked to death or hepatic failure requiring with TPV/r. HSRs reported.
noncirrhotic portal hypertension transplantation have been
reported. TPV/r: Contraindicated in patients with
and esophageal varices. hepatic insufficiency (Child Pugh class
When TAF, TDF, 3TC, and FTC NVP: Severe hepatotoxicity B or C).
are Withdrawn in Patients with associated with skin rash or
hypersensitivity. A 2-week NVP IDV and ATV: Jaundice due to indirect
HBV/HIV Coinfection or When hyperbilirubinemia
HBV Resistance Develops: dose escalation may reduce risk.
Patients with HBV/HIV coinfection Risk is greater for women with
may develop severe hepatic pre-NVP CD4 counts >250 cells/
flares. mm3 and men with pre-NVP CD4
counts >400 cells/mm3.
NVP should never be used for
post-exposure prophylaxis.
EFV and NVP are not
recommended in patients with
hepatic insufficiency (Child-Pugh
class B or C).
Drug Class
Adverse Effect
Hypersensitivity ABC: Contraindicated if patient NVP: Hypersensitivity syndrome N/A RAL: HSR reported when MVC: HSR
Reaction is HLA-B*5701 positive. of hepatotoxicity and rash RAL is given with other reported as part
that may be accompanied by drugs also known to cause of a syndrome
Excluding Median onset for HSR is 9 days; fever, general malaise, fatigue, HSRs. All ARVs should be related to
rash alone or 90% of reactions occur within first myalgias, arthralgias, blisters, stopped if HSR occurs. hepatotoxicity.
Stevens-Johnson 6 weeks of treatment. oral lesions, conjunctivitis, facial
syndrome edema, eosinophilia, renal DTG: Reported in <1%
HSR Symptoms (in Order of of patients in clinical
Descending Frequency): Fever, dysfunction, granulocytopenia, or
development program
rash, malaise, nausea, headache, lymphadenopathy.
myalgia, chills, diarrhea, vomiting, Risk is greater for ARV-naive
abdominal pain, dyspnea, women with pre-NVP CD4 counts
arthralgia, and respiratory >250 cells/mm3 and men with pre-
symptoms NVP CD4 counts >400 cells/mm3.
Symptoms worsen with Overall, risk is higher for women
continuation of ABC. than men.
Patients should not be A 2-week dose escalation of NVP

rechallenged with ABC if HSR reduces risk.
is suspected, regardless of their
HLA-B*5701 status.
Lactic Acidosis Reported with NRTIs, Especially N/A N/A N/A N/A
d4T, ZDV, and ddI: Insidious
onset with GI prodrome, weight
loss, and fatigue. May rapidly
progress with tachycardia,
tachypnea, jaundice, weakness,
mental status changes,
pancreatitis, and organ failure.
Mortality high if serum lactate >10
mmol/L.
Women and obese patients at
increased risk.
Lipodystrophy Lipoatrophy: d4T > ZDV. N/A
More likely when NRTIs are Lipohypertrophy: Trunk fat increase observed with EFV-, PI-, and RAL-containing regimens; however,
coadministered with EFV than causal relationship has not been established.
with an RTV-boosted PI.
Drug Class
Adverse Effect
Myopathy/ ZDV: Myopathy N/A N/A RAL and DTG: ↑ CPK, N/A
Elevated Creatine rhabdomyolysis, and
Phosphokinase myopathy or myositis have
been reported.
Nervous System/ d4T > ddI: Peripheral neuropathy Neuropsychiatric Events: EFV > N/A All INSTIs: Insomnia, N/A
Psychiatric (can be irreversible) RPV, DOR > ETR depression, and suicidality
Effects have been reported with
d4T: Associated with rapidly EFV: Somnolence, insomnia, INSTI use, primarily in
progressive, ascending abnormal dreams, dizziness, patients with pre-existing
neuromuscular weakness impaired concentration, psychiatric conditions.
resembling Guillain-Barré depression, psychosis, and
syndrome (rare) suicidal ideation. Symptoms
usually subside or diminish after
2–4 weeks. Bedtime dosing may
reduce symptoms. Risk factors
include presence of psychiatric
illness, concomitant use of agents
with neuropsychiatric effects, and
increased EFV concentrations
because of genetic factors or
increased absorption with food.
An association between EFV
and suicidal ideation, suicide,
and attempted suicide was found
in a retrospective analysis of
comparative trials.
RPV: Depression, suicidality,
sleep disturbances
DOR: Sleep disorders and
disturbances, dizziness, altered
sensorium; depression and
suicidality/self-harm
Rash FTC: Hyperpigmentation All NNRTIs ATV, DRV, FPV, LPV/r, and TPV All INSTIs MVC, IBA
Drug Class
Adverse Effect
Renal Effects/ TDF: ↑ SCr, proteinuria, RPV: Inhibits Cr secretion ATV and LPV/r: Associated with DTG, COBI (as a Boosting IBA: SCr
Urolithiasis hypophosphatemia, urinary without reducing renal glomerular increased risk of chronic kidney Agent for EVG), and BIC: abnormalities
phosphate wasting, glycosuria, function. disease in a large cohort study. Inhibits Cr secretion without ≥Grade 3 reported
hypokalemia, and non-anion gap reducing renal glomerular in 10% of trial
metabolic acidosis. Concurrent IDV: ↑ SCr, pyuria, renal atrophy, or function participants.
use of TDF with COBI- or RTV- hydronephrosis
containing regimens appears to IDV, ATV: Stone or crystal formation.
increase risk. Adequate hydration may reduce risk.
TAF: Less impact on renal COBI (as a Boosting Agent for DRV
biomarkers and lower rates of or ATV): Inhibits Cr secretion without
proteinuria than TDF. reducing renal glomerular function.
Stevens-Johnson Some reported cases for ddI and NVP > DLV, EFV, ETR, RPV Some reported cases for FPV, DRV, RAL N/A
Syndrome/ ZDV. IDV, LPV/r, and ATV.
Toxic Epidermal
Necrosis
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART= antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/r = atazanavir/ritonavir; BIC = bictegravir; BMD = bone
mineral density; CD4 = CD4 T lymphocyte; Cr = creatinine; CNS = central nervous system; COBI = cobicistat; CPK = creatine phosphokinase; CVD = cardiovascular disease; d4T =
stavudine; ddI = didanosine; DLV = delavirdine; DOR = doravirine; DRV = darunavir; DRV/r = darunavir/ritonavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; EI = entry
inhibitor; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; GI = gastrointestinal; HBV =
hepatitis B virus; HDL = high-density lipoprotein; HSR = hypersensitivity reaction; IBA = ibalizumab; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein;
LPV/r = lopinavir/ritonavir; MI = myocardial infarction; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase
inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SCr = serum creatinine; SQV = saquinavir; SQV/r = saquinavir/ritonavir; TAF =
tenofovir alafenamide; TC = total cholesterol; TDF = tenofovir disoproxil fumarate; TG = triglycerides; TPV = tipranavir; TPV/r = tipranavir/ritonavir; ZDV = zidovudine
Table 16. Antiretroviral Therapy-Associated Adverse Events That Can Be Managed with Substitution
of Alternative Antiretroviral Agent (page 1 of 3)
ARV Agent(s) or Drug Class

Adverse Event Comments
Switch from Switch to
Bone Density TDFa TAF or ABCb Declines in BMD have been observed upon
Effects initiation of most ART regimens. Switching
NRTI-sparing regimens or from TDF to alternative ARV agents has been
regimens using only 3TC or shown to increase bone density, but the clinical
FTC as the NRTI may be significance of this increase remains uncertain.
considered, if appropriate.
TAF is associated with smaller declines in BMD
than TDF, and patients show improvement in
BMD upon switching to TAF. The long-term
impact of TAF on patients with osteopenia
or osteoporosis is unknown; close clinical
monitoring is recommended in this setting.
Bone Marrow ZDV TDF, TAF, or ABCb ZDV has been associated with neutropenia and
Suppression macrocytic anemia.
Cardiac EFV, RPV A PI- or INSTI-based regimen High EFV and RPV exposures may cause QT
QTc Interval prolongation.
Prolongation
Consider switching from EFV- or RPV-based
regimens if patient is taking other medications
with known risk of Torsades de Pointes, or in
patients at higher risk of Torsades de Pointes.
Cardiovascular ABC TDF, TAF, FTC, or 3TC ABC use has been associated with CV disease
Events and cardiac events in some, but not all,
observational studies.
Myocardial
infarction, ischemic TDF has been associated with lower lipid levels
stroke than TAF.
RTV- or COBI-boosted PI RAL, DTG, BIC, or RPV RAL, DTG, BIC, and RPV have less effect on
regimens, EFV, EVG/c lipids than RTV- or COBI-boosted PI regimens,
EFV, and EVG/c.
Large observation cohorts have found an
association between some PIs (DRV, FPV, IDV,
LPV/r) and an increased risk of CV events.
However, this association has not been seen
with ATV. Further study is needed.
Central Nervous EFV, RPV ETR, PI/c, or PI/r In most patients, EFV-related CNS effects
System, subside within 4 weeks after initiation of the
Neuropsychiatric INSTIs may be used, but drug. Persistent or intolerable effects should
Side Effects monitoring is recommended prompt substitution of EFV.
(see Comments column).
Dizziness, suicidal INSTIs are associated with insomnia.
ideation, abnormal Depression and suicidality have been
dreams, depression infrequently reported with INSTI use, primarily
in patients with pre-existing psychiatric
conditions.
Dyslipidemia RTV- or COBI-boosted RAL, DTG, BIC, or RPV Elevated TG and LDL levels are more common
regimens, and EFV with LPV/r and FPV/r than with other RTV-
Hypertriglyceridemia boosted PIs. Improvements in TG and LDL
(with or without levels have been observed with switch from
elevated LDL level) LPV/r to ATV or ATV/r.c

Gastrointestinal LPV/r ATV/c, ATV/r, DRV/c, DRV/r, GI intolerance is common with boosted PIs
Effects RAL, DTG, BIC, or EVG/c and is linked to the total dose of RTV. More GI
toxicity is seen with LPV/r than with ATV/r or
Nausea, diarrhea DRV/r. GI effects are often transient and do not
warrant substitution unless they are persistent
and intolerable.
Other RTV- or COBI-boosted RAL, DTG, BIC, or NNRTIs In a trial of treatment-naive patients, rates of
regimens diarrhea and nausea were similar for EVG/c/
TDF/FTC and ATV/r plus TDF/FTC.
Hypersensitivity ABC TDF or TAF Never rechallenge with ABC following a
Reaction suspected HSR, regardless of the patient’s
HLA-B*5701 status.
NVP, EFV, ETR, RPV Non-NNRTI ART Risk of HSR with NVP is higher for women and
those with high CD4 cell counts.
DTG, RAL Non-INSTI ART Reactions to NVP, ETR, RAL, DTG, and
MVC Suitable alternative ART MVC may be accompanied by elevated liver
transaminases.
Insulin Resistance LPV/r, FPV/r INSTI, NNRTI Results of switch studies have been
inconsistent. Studies in HIV-negative patients
suggest a direct causal effect of LPV/r (and
IDV) on insulin resistance. However, traditional
risk factors may be stronger risk factors for
insulin resistance than the use of any PI.
Jaundice and ATV, ATV/c, ATV/r DRV/c, DRV/r, INSTI, or Increases in unconjugated bilirubin are
Icterus NNRTI common with ATV and generally do not require
modification of therapy unless resultant
symptoms are distressing to the patient.
Lipoatrophy d4T, ZDV TDF, TAF, or ABCb Peripheral lipoatrophy is associated with
prior thymidine analog (d4T and ZDV) use.
Subcutaneous fat Switching from these ARVs prevents worsening
wasting of limbs, lipoatrophy, but fat recovery is typically slow
face, buttocks (may take years) and incomplete.
Lipohypertrophy Accumulation of visceral, truncal, dorsocervical, and breast fat has been observed during ART, particularly during
use of older PI-based regimens (e.g., IDV), but whether ART directly causes fat accumulation remains unclear.
There is no clinical evidence that switching to another first line regimen will reverse weight or visceral fat gain.
Rash NNRTIs (especially NVP and PI- or INSTI-based regimen Mild rashes that develop after initiation
EFV) of NNRTIs other than NVP rarely require
treatment switch. When serious rash develops
due to any NNRTI, switch to another drug
class.
DRV/c, DRV/r ATV/c, ATV/r, or another drug Mild rashes following DRV/r use may resolve
class (e.g., INSTI) without modification of therapy. For more
severe reactions, change to an alternative
boosted PI or an agent from another drug class.

Renal Effects TDFa ABC, TAF (for patients with
b
TDF may cause tubulopathy.
CrCl >30 mL/min), NRTI-
Including proximal sparing regimens, or regimens Switching from TDF to TAF is associated
renal tubulopathy using only 3TC or FTC as the with improvement in proteinuria and renal
and elevated NRTI may be considered if biomarkers. The long-term impact of TAF
creatinine appropriate. on patients with pre-existing renal disease,
including overt proximal tubulopathy, is
unknown, and close clinical monitoring is
recommended in this setting.
ATV/c, ATV/r, LPV/r DTG, BIC, RAL, or NNRTI COBI, DTG, BIC, and, to a lesser extent,
RPV, can increase SCr through inhibition of
creatinine secretion. This effect does not affect
glomerular filtration. However, assess patient
for renal dysfunction if SCr increases by >0.4
mg/dL.
Stones ATV, ATV/c, ATV/r DRV/c, DRV/r, INSTI, or This switch should be made if the clinician
NNRTI believes ATV is the cause of the stones.
Nephrolithiasis and
cholelithiasis
a
In patients with chronic active HBV infection, another agent that is active against HBV should be substituted for TDF.
b
ABC should be used only in patients known to be HLA-B*5701 negative.
c
TDF reduces ATV levels; therefore, unboosted ATV should not be coadministered with TDF.
atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; BMD = bone mineral density; CD4 = CD4 T lymphocyte; CNS =
central nervous system; COBI = cobicistat; CrCl = creatine clearance; CV = cardiovascular; d4T = stavudine; DOR = doravirine; DRV
= darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c =
elvitegravir/cobicistat; FPV = fosamprenavir; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; GI = gastrointestinal; HBV = hepatitis
B virus; HSR = hypersensitivity reaction; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LDL = low-density lipoprotein; LPV/r
= lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase
inhibitor; NVP = nevirapine; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; RAL = raltegravir;
RPV = rilpivirine; RTV = ritonavir; SCr = serum creatinine; TAF = tenofovir alafenamide; TC = total cholesterol; TDF = tenofovir disoproxil
fumarate; TG = triglycerides; ZDV = zidovudine

Table 17. Monthly Average Prices of Commonly Used Antiretroviral Drugs (Last updated October 25, 2018; last reviewed October 25, 2018)
(page 1 of 5)
Prescription drug pricing in the United States involves complex systems of negotiations, rebates, discounts, and reimbursement rates. Much of the
information used to determine drug prices is confidential, and prices can vary depending on the purchaser, the type of public or private insurance
coverage in use, and the number of generic competitors. In addition, price increases that exceed rates of inflation can trigger additional rebates for
Medicaid and 340B Drug Discount Program entities. Table 17 includes three benchmark prices, rounded to the nearest dollar, for commonly used
antiretroviral (ARV) drugsa as a general reference for health care providers when considering the cost of HIV treatment. Health care providers
should contact patients’ pharmacies or payors regarding actual prices, comparative cost savings, and related formulary restrictions.
Wholesale acquisition cost (WAC) is the list price published by manufacturers for prescription drugs or biologics sold to wholesalers. The WAC
price approximates what retail pharmacies pay wholesalers for single-source (e.g., brand-name) drugs. There is a range of WAC prices for generic
ARVs, as these are multiple-source products with variable list prices. With increasing competition, actual transactional prices of generic drugs
among wholesalers and pharmacies decrease substantially. Average wholesale price (AWP) has historically been used as the basis for setting
public (e.g., Medicaid) and private (e.g., commercial insurer) reimbursement rates for pharmacies. Neither WAC nor AWP include variable price
concessions along supply and payment chains, including discounts and rebates to wholesalers, pharmacies, federal purchasers (e.g., the Veterans’
Administration), pharmacy benefit managers, commercial insurers, Medicaid, 340B pharmacies, and AIDS Drug Assistance Programs. The
availability of these discounts and rebates depends on product demand, market competition, and WAC price increases set by manufacturers.
Maximum prices are assigned to generic products with three or more therapeutically and pharmaceutically equivalent products, as determined
by the Food and Drug Administration. This federally established price is the federal upper limit (FUL). Federal Medicaid will reimburse state
Medicaid programs up to this limit for multiple-source drugs (plus the dispensing fee); commercial insurers set their own reimbursement upper
limits with pharmacies. Whereas WACs and AWPs are generally set annually, FULs are adjusted monthly, particularly for multiple-source drugs
with fluctuating pharmacy acquisition costs. In the table below, the FUL for a drug is described as “pending” if a generic drug currently lacks the
competition required to trigger a FUL.
ARV Drug Tablets, Capsules, or WAC AWP FUL

Strength, Formulation
(Generic and Brand Names) mLs per Month (Monthly)b (Monthly)b (As of 9/1/2018)c
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Abacavir
• Generic 300 mg tablet 60 tablets $150 to $482 $579 to $603 $44
• Ziagen 300 mg tablet 60 tablets $559 $670
Emtricitabine
• Emtriva 200 mg capsules 30 capsules $537 $644 N/A
Lamivudine
• Epivir 300 mg tablet 30 tablets $416 $499
45
(page 2 of 5)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs), continued
Tenofovir Disoproxil Fumarate
• Generic 300 mg tablet 30 tablets $58 to $922 $110 to $1,216 Pending
•V iread 300 mg tablet 30 tablets $1,140 $1,368
Zidovudine
•G eneric 300 mg tablet 60 tablets $36 to $54 $54 to $365 $13
NRTI Combination Products
Abacavir/Lamivudine
•G eneric 600 mg/300 mg tablets 30 tablets $185 to $1,116 $1,395 $356
• Epzicom 600 mg/300 mg tablets 30 tablets $1,292 $1,550
Tenofovir Alafenamide/Emtricitabine
• Descovy 25 mg/200 mg tablet 30 tablets $1,676 $2,011 N/A
Tenofovir Disoproxil Fumarate/Emtricitabine
•T ruvada 300 mg/200 mg tablet 30 tablets $1,676 $2,011 N/A
Tenofovir Disoproxil Fumarate/Lamivudine
• Cimduo 300 mg/300 mg tablet 30 tablets $1,005 $1,207 N/A
Zidovudine/Lamivudine
•G eneric 300 mg/150 mg tablet 60 tablets $134 to $578 $878 to $932 $47
•C ombivir 300 mg/150 mg tablet 60 tablets $901 $1,082
Abacavir Sulfate/Zidovudine/Lamivudine
•G eneric 300 mg/300 mg/150 mg tablet 60 tablets $1,391 $1,738 Pending
• Trizivir 300 mg/300 mg/150 mg tablet 60 tablets $1,610 $1,932
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Efavirenz
• Generic 600 mg tablet 30 tablets $894 $1,118 Pending
• Sustiva 600 mg tablet 30 tablets $981 $1,177
Doravirine
• Pifeltro 100 mg tablet 30 tablets $1,380 $1,656 N/A
46
(page 3 of 5)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), continued
Etravirine
• Intelence 200 mg tablet 60 tablets $1,296 $1,523 N/A
Nevirapine
• Viramune 200 mg tablet 60 tablets $855 $1,026
• Generic XR 400 mg tablet 30 tablets $246 to $565 $678 to $706
$231
• Viramune XR 400 mg tablet 30 tablets $793 $951
Rilpivirine
•E durant 25 mg tablet 30 tablets $1043 $1,252 N/A
Protease Inhibitors (PIs)
Atazanavir
• Generic 200 mg capsule 60 capsules $878 to $1,264 $1,580 to $1,668 Pending
• Reyataz 200 mg capsule 60 capsules $1,463 $1,756
• Generic 300 mg capsule 30 capsules $870 to $1,252 $1,565 to $1,652
Pending
• Reyataz 300 mg capsule 30 capsules $1,449 $1,739
Atazanavir/Cobicistat
• Evotaz 300/150 mg tablet 30 tablets $1,605 $1,927 N/A
Darunavir
• Prezista 600 mg tablet 60 tablets $1,581 $1,897 N/A
• Prezista 800 mg tablet 30 tablets $1,581 $1,897 N/A
• Prezista 100 mg/mL suspension 200 mL $878 $1,054 N/A
Darunavir/Cobicistat
• Prezcobix 800 mg/150 mg tablet 30 tablets $1,806 $2,168 N/A
Lopinavir/Ritonavir
• Kaletra 200 mg/50 mg tablet 120 tablets $1,024 $1,229 N/A
Tipranavir
•A ptivus 250 mg capsule 120 capsules $1,578 $1,894 N/A
47
(page 4 of 5)
Integrase Strand Transfer Inhibitors (INSTIs)
Dolutegravir
• Tivicay 50 mg tablet 30 tablets $1,658 $1,989 N/A
• Tivicay 50 mg tablet 60 tablets $3,315 $3,978 N/A
Raltegravir
• Isentress 400 mg tablet 60 tablets $1,500 $1,800 N/A
• Isentress HD 600 mg tablet 60 tablets $1,500 $1,800 N/A
Fusion Inhibitor
Enfuvirtide
• Fuzeon 90 mg injection kit 60 doses (1 kit) $3,586 $4,303 N/A
CCR5 Antagonist
Maraviroc
• Selzentry 150 mg tablet 60 tablets $1,511 $1,813 N/A
CD4-Directed Post-Attachment Inhibitor
Ibalizumab-uiyk
• Trogarzo 200 mg vials 8 vials $9,080 $10,896 N/A
Coformulated Combination Products as Single Tablet Regimens
Bictegravir/Tenofovir Alafenamide/Emtricitabine
• Biktarvy 50 mg/25 mg/200 mg 30 tablets $2,946 $3,535 N/A
Darunavir/Cobicistat/Tenofovir Alafenamide/Emtricitabine
• Symtuza 600 mg/150 mg/10 mg/200 mg 30 tablets $3,482 $4,178 N/A
Dolutegravir/Abacavir/Lamivudine
•T riumeq 50 mg/600 mg/300 mg tablet 30 tablets $2,805 $3,366 N/A
Dolutegravir/Rilpivirine
• Juluca 50 mg/25 mg 30 tablets $2,579 $3,095 N/A
Doravirine/Tenofovir Disoproxil Fumarate/Lamivudine
• Delstrigo 100 mg/300 mg/300 mg 30 tablets $2,100 $2,520 N/A
48
(page 5 of 5)
Coformulated Combination Products as Single Tablet Regimens, continued
Efavirenz/Tenofovir Disoproxil Fumarate/Emtricitabine
• Atripla 600 mg/300 mg/200 mg tablet 30 tablets $2,724 $3,269 N/A
Efavirenz/Tenofovir Disoproxil Fumarate/Lamivudine
• Symfi 600 mg/300 mg/300 mg tablet 30 tablets $1,634 $1,961 N/A
• Symfi Lo 400 mg/300 mg/300 mg tablet 30 tablets $1,634 $1,961 N/A
Elvitegravir/Cobicistat/Tenofovir Alafenamide/Emtricitabine
•G envoya 150 mg/150 mg/10 mg/200 mg tablet 30 tablets $2,946 $3,535 N/A
Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/
Emtricitabine
•S tribild 150 mg/150 mg/300 mg/200 mg tablet 30 tablets $3,090 $3,708 N/A
Rilpivirine/Tenofovir Alafenamide/Emtricitabine
• Odefsey 25 mg/25 mg/200 mg tablet 30 tablets $2,681 $3,217 N/A
Rilpivirine/Tenofovir Disoproxil Fumarate/Emtricitabine
•C
omplera 25 mg/300 mg/200 mg tablet 30 tablets $2,681 $3,217 N/A
Pharmacokinetic Enhancers (Boosters)
Cobicistat
•T
ybost 150 mg tablet 30 tablets $219 $264 N/A
Ritonavir
•G
eneric 100 mg tablet 30 tablets $222 $278 Pending
• Norvir 100 mg tablet 30 tablets $257 $309
a
The following less commonly used ARV drugs are not included in this table: delavirdine, didanosine, fosamprenavir, indinavir, nelfinavir, saquinavir, and stavudine.
b
Source: IBM Watson Health. Micromedex Red Book [database]. 2018. Available at: https://www.micromedexsolutions.com
c
ource: Medicare & Medicaid Services. Federal Upper Limits—September 2018 [database]. 2018 September 1. Available at: https://www.medicaid.gov/medicaid/prescription-drugs/
S
pharmacy-pricing/index.html.
49
Table 18. Mechanisms of Antiretroviral-Associated Drug Interactions (Last updated October 25,
2018; last reviewed October 25, 2018) (page 1 of 2)
PK interactions may occur during absorption, metabolism, or elimination of the ARV and/or the interacting
drugs. This table does not include a comprehensive list of all possible mechanisms of interactions for
individual ARV drugs (e.g., transporters); however, the table lists the most common mechanisms of known
interactions and focuses on absorption and CYP- and UGT1A1-mediated interactions.
Note: N/A indicates that there are no clinically relevant interactions by these mechanisms. Identified
mechanisms are specific to individual ARV drugs and not combinations of ARV drugs.
Mechanisms That May Affect Oral Enzymes That Metabolize or are Induced or Other
ARV
Absorption of ARV Drugs Inhibited by ARV Drugs Mechanisms
Drugs
of Known
by Drug Increasing Cationic P-glyco- CYP CYP CYP
UGT1A1 Drug
Class Gastric pH Chelation protein Substrate Inhibitor Inducer Interactions
INSTIs
BIC N/A Concentration Substrate 3A4 N/A N/A Substrate Inhibitor of renal
decreased transporters
by products OCT2 and
that contain MATE1
DTG N/A polyvalent Substrate 3A4 (minor) N/A N/A Substrate Inhibitor of renal
cations (e.g., transporters
Ca, Mg, Al, Fe, OCT2 and
Zn) MATE1
EVG N/A N/A 3A4 N/A 2C9 Substrate N/A
RAL N/A N/A N/A N/A N/A Substrate N/A
PK Enhancers (Boosters)
COBI N/A N/A Inhibitor 3A4 3A4, 2D6 N/A N/A N/A
RTV N/A N/A Substrate, 3A4, 2D6 3A4, 2D6 1A2, 2B6, Inducer N/A
inhibitor 2C8, 2C9,
2C19
PIs
Note: When PIs are coadministered with PK enhancers (boosters), the pharmacologic properties of both agents should be considered
when assessing potential drug interactions.
ATV Concentration N/A Substrate, 3A4 3A4 N/A Inhibitor OATP inhibitor
decreased inducer,
inhibitor
DRV N/A N/A Substrate, 3A4 3A4 2C9 N/A OATP inhibitor
inducer
FPV Concentration N/A Substrate, 3A4 3A4 N/A N/A N/A
decreased by inhibitor
H2 antagonist
LPV N/A N/A Substrate 3A4 3A4 N/A N/A OATP inhibitor
SQV N/A N/A Substrate, 3A4 3A4 N/A N/A OATP inhibitor
inhibitor
TPV N/A N/A Substrate, 3A4 2D6 3A4, 1A2, N/A OATP inhibitor
inducer 2C19
NNRTIs
DOR N/A N/A N/A 3A4, 3A5 N/A N/A N/A N/A
EFV N/A N/A N/A 2B6 3A4 3A4, 2B6, N/A N/A
(primary), 2C19
2A6, 3A4

Table 18. Mechanisms of Antiretroviral-Associated Drug Interactions (Last updated October 25,
Mechanisms That May Affect Oral Enzymes That Metabolize or are Induced or Other
ARV
Absorption of ARV Drugs Inhibited by ARV Drugs Mechanisms
Drugs
of Known
by Drug Increasing Cationic P-glyco- CYP CYP CYP
UGT1A1 Drug
Class Gastric pH Chelation protein Substrate Inhibitor Inducer Interactions
NNRTIs, continued
ETR N/A N/A N/A 3A4, 2C9, 2C9, 2C19 3A4 N/A N/A
2C19
NVP N/A N/A N/A 3A4, 2B6 N/A 3A4, 2B6 N/A N/A
RPV Concentration N/A N/A 3A4 N/A N/A N/A N/A
decreased
NRTIs
ABC N/A N/A N/A N/A N/A N/A Substrate Alcohol
dehydrogenase
substrate
FTC N/A N/A N/A N/A N/A N/A N/A N/A
3TC N/A N/A N/A N/A N/A N/A N/A N/A
TAF N/A N/A Substrate N/A N/A N/A N/A OATP substrate
TDF N/A N/A Substrate N/A N/A N/A N/A Competition
of active
renal tubular
secretion
ZDV N/A N/A N/A N/A N/A N/A N/A Glucuronidation
CCR5 Antagonist
MVC N/A N/A Substrate 3A4 N/A N/A N/A N/A
Fusion Inhibitor
T-20 N/A N/A N/A N/A N/A N/A N/A N/A
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; Ca
= calcium; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR
= etravirine; EVG = elvitegravir; Fe = iron; FPV = fosamprenavir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LPV
= lopinavir; MATE = multidrug and toxin extrusion transporter; Mg = magnesium; MVC = maraviroc; NNRTI = non-nucleoside reverse
transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; NVP = nevirapine; OCT2 = organic cation transporter 2;
OATP = organic anion-transporting polypeptide; PK = pharmacokinetic; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV =
ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; UGT =
uridine diphosphate glucuronosyltransferase; ZDV = zidovudine; Zn = zinc

Table 19a. Drug Interactions Between Protease Inhibitors and Other Drugs (Last updated October 25,
This table provides known or predicted information regarding PK interactions between PIs and non-ARV
drugs. When information is available, interactions for PK-boosted (with either RTV or COBI) and unboosted
ATV are listed separately. The term “All PIs” refers to both unboosted ATV and PIs boosted with either RTV
or COBI, except the PIs noted below. For interactions between ARV agents and for dosing recommendations,
refer to Tables 19c, 20a, and 20b.
Recommendations for managing a particular drug interaction may differ depending on whether a new ARV
drug is being initiated in a patient on a stable concomitant medication or if a new concomitant medication is
being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are
difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly.
Note: FPV, IDV, NFV, and SQV are not included in this table. Please refer to the FDA product labels for
FPV, IDV, NFV, and SQV for information regarding drug interactions with these PIs.
Effect on PI and/
Concomitant
PI or Concomitant Drug Dosing Recommendations and Clinical Comments
Drug
Concentrations
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin All PIs ↑ alfuzosin expected Contraindicated.
Doxazosin All PIs ↑ doxazosin possible Initiate doxazosin at lowest dose and titrate while monitoring for
clinical response/toxicity. Dose reduction may be necessary.
Tamsulosin All PIs ↑ tamsulosin expected Coadministration is not recommended. If coadministered,
monitor for tamsulosin toxicities.
Terazosin All PIs ↔ or ↑ terazosin possible Initiate terazosin at lowest dose and titrate while monitoring for
clinical response/toxicity. Dose reduction may be necessary.
Silodosin All PIs ↑ silodosin expected Contraindicated.
Acid Reducers
Antacids ATV, ATV/c, When given simultaneously, ↓ Give ATV at least 2 hours before or 1–2 hours after antacids or
ATV/r ATV expected buffered medications.
TPV/r TPV AUC ↓ 27% Give TPV at least 2 hours before or 1 hour after antacids.
H2 Receptor ATV ↓ ATV H2 receptor antagonist single dose should not exceed a dose
Antagonists (unboosted) equivalent to famotidine 20 mg, and the total daily dose should
not exceed a dose equivalent to famotidine 20 mg BID in PI-naive
patients. Unboosted ATV plus famotidine should not be used in
combination in PI-experienced patients.
Give ATV at least 2 hours before and at least 10 hours after the
H2 receptor antagonist.
ATV/c, ATV/r ↓ ATV H2 receptor antagonist dose should not exceed a dose equivalent
to famotidine 40 mg BID in ART-naive patients or famotidine 20
mg BID in ART-experienced patients.
Give ATV 300 mg plus (COBI 150 mg or RTV 100 mg)
simultaneously with and/or ≥10 hours after the dose of H2
receptor antagonist.
If using TDF and H2 receptor antagonist in ART-experienced
patients, use ATV 400 mg plus (COBI 150 mg or RTV 100 mg).
DRV/c, DRV/r, ↔ demonstrated or expected No dose adjustment necessary.
LPV/r

Table 19a. Drug Interactions Between Protease Inhibitors and Other Drugs (Last updated October
25, 2018; last reviewed October 25, 2018) (page 2 of 19)
Effect on PI and/
Concomitant
Drug
Concentrations
Acid Reducers, continued
PPIs ATV ↓ ATV PPIs are not recommended in patients receiving unboosted
(unboosted) ATV. In these patients, consider alternative acid-reducing agents,
RTV or COBI boosting, or alternative PIs.
ATV/c, ATV/r ↓ ATV PPIs should not exceed a dose equivalent to omeprazole 20 mg
daily in PI-naive patients.
PPIs should be administered at least 12 hours before ATV/c or
ATV/r.
PPIs are not recommended in PI-experienced patients.
DRV/c, LPV/r ↔ expected No dose adjustment necessary.
DRV/r Omeprazole AUC ↓ 42% No dose adjustment necessary. If there is a lack of symptomatic
relief, increase dose to no more than omeprazole 40 mg daily.
TPV/r Omeprazole AUC ↓ 70% Coadministration is not recommended. If coadministration is
necessary, dose increases of omeprazole may be considered
based on clinical response.
Anticoagulants and Antiplatelets
Apixaban PI/c, PI/r ↑ apixaban expected Coadministration is not recommended in patients who require
apixaban 2.5 mg twice daily.
In patients who require apixaban 5 mg or 10 mg twice daily,
reduce apixaban dose by 50%.
Betrixaban ATV/c, ATV/r, ↑ betrixaban expected Administer an initial single dose of betrixaban 80 mg followed by
LPV/r betrixaban 40 mg once daily.
DRV/c, DRV/r ↔ betrixaban expected No dose adjustment necessary.
TPV/r No data No dosing recommendations available at this time. Consider
alternative ARV or warfarin.
Dabigatran ATV/c, ATV/r, ↑ dabigatran expected Dabigatran dosing recommendation depends on indication
LPV/r and renal function. Refer to dabigatran dosing instructions for
With COBI 150 mg Alone: concomitant use with P-gp inhibitors in dabigatran prescribing
•D
abigatran AUC ↑ 110% to information.
127%
DRV/c, DRV/r ↔ dabigatran expected No dose adjustment necessary.
Edoxaban ATV/c, ATV/r, ↑ edoxaban expected Stroke Prevention in Nonvalvular Atrial Fibrillation Indication:
LPV/r • No dose adjustment necessary.
Deep Venous Thrombosis and Pulmonary Embolism Indication:
• Administer edoxaban 30 mg once daily
DRV/c, DRV/r ↔ edoxaban expected No dose adjustment necessary.
Rivaroxaban PI/c, PI/r ↑ rivaroxaban expected Coadministration is not recommended.
Ticagrelor All PIs ↑ ticagrelor expected Coadministration is not recommended.
Vorapaxar All PIs ↑ vorapaxar expected Coadministration is not recommended.

Effect on PI and/
Concomitant
Drug
Concentrations
Anticoagulants and Antiplatelets, continued
Warfarin PI/r ↓ warfarin possible Monitor INR closely when stopping or starting PI/c and adjust
PI/c No data warfarin dose accordingly. If switching between RTV and COBI,
the effect of COBI on warfarin is not expected to be equivalent to
RTV’s effect on warfarin.
Anticonvulsants
Carbamazepine ATV May ↓ PI levels substantially Do not coadminister. Consider alternative anticonvulsant or
(unboosted) ARV.
ATV/r, LPV/r, ↑ carbamazepine possible Consider alternative anticonvulsant or monitor levels of both
TPV/r drugs and assess virologic response. Do not coadminister with
TPV/r ↑ carbamazepine AUC LPV/r once daily.
26%
May ↓ PI levels substantially
DRV/r Carbamazepine AUC ↑ 45% Monitor anticonvulsant level and adjust dose accordingly.
DRV: no significant change
PI/c ↑ carbamazepine possible Contraindicated.
↓ cobicistat expected
↓ PI levels expected
Eslicarbazepine, All PIs ↓ PI possible Consider alternative anticonvulsant or ARV. If coadministration is
Oxcarbazepine necessary, monitor for virologic response. Consider monitoring
anticonvulsant and PI concentration.
Ethosuximide All PIs ↑ ethosuximide possible Clinically monitor for ethosuximide toxicities.
Lamotrigine ATV Lamotrigine: no effect No dose adjustment necessary.
(unboosted)
ATV/r Lamotrigine AUC ↓ 32% A dose increase of lamotrigine may be needed; consider
LPV/r Lamotrigine AUC ↓ 50% monitoring lamotrigine concentration or consider alternative
anticonvulsant.
LPV: no significant change
DRV/r, TPV/r ↓ lamotrigine possible
PI/c No data Monitor anticonvulsant level and adjust dose accordingly.
Phenobarbital PI/c ↓ cobicistat expected Contraindicated.
ATV May ↓ PI levels substantially Consider alternative anticonvulsant or monitor levels of both
(unboosted), drugs and assess virologic response.
PI/r
Do not coadminister with LPV/r once daily or unboosted ATV.

Effect on PI and/
Concomitant
Drug
Concentrations
Anticonvulsants, continued
Phenytoin ATV May ↓ PI levels substantially Do not coadminister. Consider alternative anticonvulsant or
(unboosted) ATV/r.
ATV/r, DRV/r, ↓ phenytoin possible Consider alternative anticonvulsant or monitor levels of both
TPV/r drugs and assess virologic response.
↓ PI possible
LPV/r Phenytoin AUC ↓ 31% Consider alternative anticonvulsant or monitor levels of both
drugs and assess virologic response.
LPV/r AUC ↓ 33%
Do not coadminister with LPV/r once daily.
PI/c ↓ cobicistat expected Contraindicated.
Valproic Acid PI/c, PI/r ↓ or ↔VPA possible Monitor VPA levels and virologic response. Monitor for LPV-
(VPA) related toxicities.
LPV AUC ↑ 75%
Antidepressants, Anxiolytics, and Antipsychotics (also see Sedative/Hypnotics section below)
Aripiprazole PI/c, PI/r ↑ aripiprazole expected Administer 25% of the usual aripiprazole dose. Titrate dose based
on clinical monitoring for efficacy/toxicity. Refer to aripiprazole
label for doses to use in patients who have major depressive
disorder or who are known to be CYP2D6 poor metabolizers.
ATV ↑ aripiprazole expected Administer 50% of the usual aripiprazole dose. Titrate based on
(unboosted) clinical monitoring for efficacy/toxicity. Refer to aripiprazole label
for doses to use in patients who have major depressive disorder
or who are known to be CYP2D6 poor metabolizers.
Brexpiprazole PI/c, PI/r ↑ brexpiprazole expected Administer 25% of the usual brexpiprazole dose. Titrate based on
clinical monitoring for efficacy/toxicity. Refer to brexpiprazole label
ATV ↑ brexpiprazole expected Administer 50% of the usual brexpiprazole dose. Titrate based on
(unboosted) clinical monitoring for efficacy/toxicity. Refer to brexpiprazole label
Bupropion LPV/r Bupropion AUC ↓ 57% Titrate bupropion dose based on clinical response.
TPV/r Bupropion AUC ↓ 46%
ATV/r, DRV/r ↓ bupropion possible
PI/c ↔ bupropion expected No dose adjustment necessary.
Buspirone All PIs ↑ buspirone expected Use a low dose of buspirone with caution and titrate buspirone
dose based on clinical response.

Effect on PI and/
Concomitant
Drug
Concentrations
Antidepressants, Anxiolytics, and Antipsychotics (also see Sedative/Hypnotics section below), continued
Cariprazine All PIs ↑ cariprazine expected Starting Cariprazine in a Patient Already Receiving a PI:
• Administer cariprazine 1.5 mg on Day 1 and Day 3, with no dose
given on Day 2. From Day 4 onward, administer cariprazine
1.5 mg daily. Dose can be increased to a maximum dose of
cariprazine 3 mg daily. If the PI is withdrawn, cariprazine dose
may need to be increased.
Starting a PI in a Patient Already Receiving Cariprazine:
• For patients receiving cariprazine 3 mg or cariprazine 6 mg
daily, reduce dose by half. For patients taking cariprazine 4.5
mg daily, the dose should be reduced to cariprazine 1.5 mg
or cariprazine 3 mg daily. For patients taking cariprazine 1.5
mg daily, change to cariprazine 1.5 mg every other day. If PI is
withdrawn, cariprazine dose may need to be increased.
Fluvoxamine All PIs ↑ fluvoxamine possible Titrate fluvoxamine dose based on clinical response.
Lurasidone PI/c, PI/r ↑ lurasidone expected Contraindicated.
ATV ↑ lurasidone expected Consider alternative therapy. If coadministration is necessary,
(unboosted) reduce lurasidone dose by 50%.
Pimavanserin All PIs ↑ pimavanserin expected Reduce dose from pimavanserin 34 mg daily to pimavanserin 17
mg daily.
Pimozide All PIs ↑ pimozide expected Contraindicated.
Quetiapine All PIs ↑ quetiapine expected Starting Quetiapine in a Patient Receiving a PI:
• Start quetiapine at the lowest dose and titrate up as needed.
Monitor for quetiapine effectiveness and adverse effects.
Starting a PI in a Patient Receiving a Stable Dose of Quetiapine:
• Reduce quetiapine dose to 1/6 of the original dose. Closely
monitor for quetiapine effectiveness and adverse effects.
Trazodone All PIs RTV 200 mg BID (for 2 days) ↑ Use lowest dose of trazodone and monitor for CNS and CV
trazodone AUC 240% adverse effects.
Tricyclic All PIs ↑ TCA expected Use lowest possible TCA dose and titrate based on clinical
Antidepressants assessment and/or drug levels.
(TCA)
Amitriptyline,
desipramine,
doxepin, imipramine,
nortriptyline
Other PI/c, PI/r ↑ antipsychotic possible Titrate antipsychotic dose using the lowest initial dose, or adjust
Antipsychotics maintenance dose accordingly. Monitor for toxicities.
(CYP3A4 and/or
CYP2D6 substrates)
Other Selective DRV/r Paroxetine AUC ↓ 39% Titrate SSRI dose based on clinical response.
Serotonin Reuptake
Sertraline AUC ↓ 49%
Inhibitors (SSRIs)
(e.g., citalopram, ATV/r, LPV/r, No data
escitalopram, TPV/r
fluoxetine, paroxetine, PI/c Effects unknown Titrate SSRI dose using the lowest available initial or
sertraline) maintenance dose.

Effect on PI and/
Concomitant
Drug
Concentrations
Antifungals
Fluconazole PI/c, ATV/r, No significant effect observed or No dose adjustment necessary.
DRV/r, LPV/r expected
TPV/r TPV AUC ↑ 50% Fluconazole >200 mg daily is not recommended. If high-dose
fluconazole is indicated, consider alternative ARV.
Isavuconazole LPV/r Isavuconazole AUC ↑ 96% If coadministered, consider monitoring isavuconazole
concentrations and toxicities and assessing virologic response.
LPV AUC ↓ 27%
RTV AUC ↓ 31%
All PIs except ↑ isavuconazole possible If coadministered, consider monitoring isavuconazole concentrations
LPV/r and toxicities. Monitor for PI toxicity and virologic response.
↑ or ↓ PI possible
Itraconazole All PIs ↑ itraconazole possible Consider monitoring itraconazole level to guide dose adjustments.
Doses >200 mg/day are not recommended with PI/r, ATV/c, or
↑ PI possible
DRV/c unless dosing is guided by itraconazole levels.
Posaconazole ATV/r ATV AUC ↑ 146% If coadministered, monitor for PI adverse effects. Consider
monitoring for posaconazole concentrations and toxicities.
↑ posaconazole possible
ATV ATV AUC ↑ 268%
ATV/c, DRV/c, ↑ PI possible
DRV/r, LPV/r,
TPV/r
Voriconazole ATV ↑ voriconazole possible Monitor for toxicities.
(unboosted)
↑ PI possible
All PI/r RTV 100 mg BID ↓ voriconazole Do not coadminister voriconazole and RTV or COBI unless
AUC 39% benefit outweighs risk. If coadministered, consider monitoring
PI/c Effect on voriconazole unknown voriconazole concentration and adjust dose accordingly.
Antihyperglycemics
Canagliflozin PI/r ↓ canagliflozin expected If a patient is already tolerating canagliflozin 100 mg daily, has
an eGFR >60 mL/min/1.73m2, and requires additional glycemic
control, consider increasing dose to canagliflozin 300 mg daily.
PI/c ↓ canagliflozin possible If used in combination, monitor glycemic control.
Saxagliptin All PIs ↑ saxagliptin expected Limit saxagliptin dose to 2.5 mg once daily
Dapagliflozin/ All PIs ↑ saxagliptin expected Do not coadminister, as this coformulated drug contains 5 mg of
Saxagliptin saxagliptin.
Antimalarials
Artemether/ DRV/r Artemether AUC ↓ 16% Clinical significance unknown. If used, monitor closely for
Lumefantrine antimalarial efficacy and lumefantrine toxicity.
DHA AUC ↓ 18%
a
Lumefantrine AUC ↑ 2.5-fold

DRV/c ↑ lumefantrine expected
Effect on artemether unknown
LPV/r Artemether AUC ↓ 40%
DHA AUC ↓ 17%
Lumefantrine AUC ↑ 470%

Effect on PI and/
Concomitant
Drug
Concentrations
Antimalarials, continued
Artesunate/ LPV/r Dihydroartemisinin AUC ↓ 49% Clinical significance unknown. If used, monitor closely for
Mefloquine antimalarial efficacy.
Mefloquine AUC ↓ 28%
↔ LPV
Atovaquone/ ATV/r, LPV/r With ATV/r: No dose recommendation. Consider alternative drug for malaria
Proguanil • Atovaquone AUC ↓ 46% prophylaxis, if possible.
• Proguanil AUC ↓ 41%
With LPV/r:
• Atovaquone AUC ↓ 74%
• Proguanil AUC ↓ 38%
Mefloquine RTV With RTV 200 mg BID: Use with caution. Effect on exposure of RTV-boosted PIs is
• RTV AUC ↓ 31%, Cmin ↓ 43% unknown.
↔ mefloquine
Antimycobacterials (for treatment of Mycobacterium tuberculosis and nontuberculosis mycobacterial infections)
Bedaquiline All PIs With LPV/r: Clinical significance unknown. Use with caution if benefit
• Bedaquiline AUC ↑ 1.9-fold outweighs the risk and monitor for QTc prolongation and liver
function tests.
With Other PI/r, ATV/c, or
DRV/c:
• ↑ bedaquiline possible
Clarithromycin ATV Clarithromycin AUC ↑ 94% May cause QTc prolongation. Reduce clarithromycin dose by
(unboosted) 50%. Consider alternative therapy (e.g., azithromycin).
All PIs ↑ clarithromycin expected Consider alternative macrolide (e.g., azithromycin).
DRV/r ↑ clarithromycin AUC 57% Monitor for clarithromycin-related toxicities or consider an
alternative macrolide (e.g., azithromycin).
LPV/r ↑ clarithromycin expected
Reduce clarithromycin dose by 50% in patients with CrCl 30−60
RTV 500 mg BID ↑ clarithromycin mL/min.
77%
Reduce clarithromycin dose by 75% in patients with CrCl <30 mL/
TPV/r ↑ clarithromycin 19% min.
Clarithromycin ↑ TPV 66%

Effect on PI and/
Concomitant
Drug
Concentrations
Antimycobacterials (for treatment of Mycobacterium tuberculosis and nontuberculosis mycobacterial infections), continued
Rifabutin ATV ↑ rifabutin AUC expected Rifabutin 150 mg once daily or 300 mg three times a week.
(unboosted)
Monitor for antimycobacterial activity and consider therapeutic
ATV/r Compared with Rifabutin (300 drug monitoring.
mg Once Daily) Alone, Rifabutin
(150 mg Once Daily) plus ATV/r: PK data reported in this table are results from healthy volunteer
• Rifabutin AUC ↑ 110% and studies. Lower rifabutin exposure has been reported in patients
metabolite AUC ↑ 2,101% with HIV than in healthy study participants.
DRV/r Compared with Rifabutin (300
mg Once Daily) Alone, Rifabutin
(150 mg Every Other Day) plus
DRV/r:
• Rifabutin AUC ↔ and
metabolite AUC ↑ 881%
LPV/r Compared with Rifabutin (300
mg daily) Alone, Rifabutin (150
mg Once Daily) plus LPV/r:
• Rifabutin AUC ↑ 203% and
metabolite AUC ↑ 375%
TPV/r Rifabutin AUC ↑ 190% and
metabolite AUC ↑ 1,971%
PI/c ↑ rifabutin expected
Rifampin All PIs ↓ PI concentration by >75% Contraindicated. Additional RTV does not overcome this
interaction and may increase hepatotoxicity. Additional COBI is
not recommended. Consider rifabutin if a rifamycin is indicated.
Rifapentine All PIs ↓ PI expected Do not coadminister.
Antipneumocystis and Antitoxoplasmosis Drug
Atovaquone ATV/r ↔ atovaquone No dose adjustment necessary.
Cardiac Medications
Amiodarone TPV/r ↑ both amiodarone and PI Contraindicated.
possible
All PIs except ↑ both amiodarone and PI Use with caution. Monitor for amiodarone toxicity and consider
TPV/r possible ECG and amiodarone drug levels.
Antiarrhythmics ATV ↑ antiarrhythmic possible Consider alternative antiarrhythmics or ARV. If coadministered,
(e.g., disopyramide, (unboosted) monitor for antiarrhythmic toxicities.
dofetilide, lidocaine, PI/c, PI/r ↑ antiarrhythmic possible Do not coadminister. Consider alternative antiarrhythmics or
mexiletine, ARV.
propafenone)
Dronedarone ATV ↑ dronedarone possible Do not coadminister.
(unboosted)
PI/c, PI/r ↑ dronedarone expected Contraindicated.
Flecanide All PIs except ↑ flecainide possible Do not coadminister.
TPV/r
TPV/r ↑ flecanide expected Contraindicated.

Effect on PI and/
Concomitant
Drug
Concentrations
Cardiac Medications, continued
Propafenone All PIs except ↑ propafenone possible Do not coadminister.
TPV/r
TPV/r ↑ propafenone expected Contraindicated.
Quinidine All PIs except ↑ quinidine possible Do not coadminister.
TPV/r
TPV/r ↑ quinidine expected Contraindicated.
Beta-Blockers All PIs ↑ beta-blockers possible May need to decrease beta-blocker dose; adjust dose based on
(e.g., carvedilol, clinical response.
metoprolol, timolol)
Consider using beta-blockers that are not metabolized by
CYP450 enzymes (e.g., atenolol, labetalol, nadolol, sotalol).
Bosentan All PIs LPV/r ↑ bosentan 48-fold (Day Do not coadminister bosentan and unboosted ATV.
4) and 5-fold (Day 10)
In Patients on a PI (Other than Unboosted ATV) >10 Days:
↓ ATV expected • Start bosentan at 62.5 mg once daily or every other day.
In Patients on Bosentan who Require a PI (Other than Unboosted
ATV):
• Stop bosentan ≥36 hours before PI initiation and restart
bosentan 10 days after PI initiation at 62.5 mg once daily or
every other day.
When Switching Between COBI and RTV:
• Maintain same bosentan dose.
Calcium Channel All PIs ↑ dihydropyridine possible Use with caution. Titrate CCB dose and monitor closely. ECG
Blockers (CCBs), monitoring is recommended when CCB is used with ATV.
Except Diltiazem ↑ verapamil possible
Digoxin PI/c , PI/r RTV (200 mg BID) ↑ digoxin Use with caution. Monitor digoxin levels. Digoxin dose may need
AUC 29% and ↑ half-life 43% to be decreased. Titrate initial digoxin dose.
DRV/r ↑ digoxin AUC 36%
COBI ↑ digoxin Cmax 41% and
↔ AUC
Diltiazem ATV/c, Unboosted ATV ↑ diltiazem AUC Decrease diltiazem dose by 50%. ECG monitoring is
ATV/r, ATV 125% recommended.
(unboosted)
Greater ↑ likely with ATV/c or
ATV/r
DRV/c, DRV/r, ↑ diltiazem possible Use with caution. Adjust diltiazem according to clinical response
LPV/r, TPV/r and toxicities.
Eplerenone PI/c, PI/r ↑ eplerenone expected Contraindicated.
Ranolazine ATV ↑ ranolazine possible Do not coadminister.
(unboosted)
PI/c, PI/r ↑ ranolazine expected Contraindicated.
Ivabradine All PIs ↑ ivabradine expected Contraindicated.

Effect on PI and/
Concomitant
Drug
Concentrations
Corticosteroids
Beclomethasone DRV/r ↔ 17-BMP (active metabolite) No dose adjustment necessary.
Inhaled or AUC
intranasal
RTV 100 mg BID ↑ 17-BMP
AUC 2-fold
All PIs except ↔ expected No dose adjustment necessary.
DRV/r
Budesonide, All PIs ↑ glucocorticoids possible Coadministration can result in adrenal insufficiency and Cushing’s
Ciclesonide, syndrome. Do not coadminister unless potential benefits of
Fluticasone, RTV 100 mg BID ↑ fluticasone inhaled or intranasal corticosteroid outweigh the risks of
Mometasone AUC 350-fold adverse effects associated with corticosteroids. Consider an
Inhaled or alternative corticosteroid (e.g., beclomethasone).
intranasal
Betamethasone, All PIs ↑ glucocorticoids possible Coadministration can result in adrenal insufficiency and Cushing’s
Budesonide syndrome. Do not coadminister unless potential benefits of
↓ PI possible
Systemic systemic corticosteroid outweigh the risks of adverse effects
associated with systemic corticosteroids.
Dexamethasone All PIs ↑ glucocorticoids possible Consider alternative corticosteroid for long-term use. If
Systemic coadministration is necessary, monitor virologic response to ART.
↓ PI possible
Prednisone, LPV/r ↑ prednisolone AUC 31% Coadministration may be considered if the potential benefits
Prednisolone All PIs ↑ prednisolone possible outweigh the risks of adverse effects associated with systemic
Systemic corticosteroids. If coadministered, monitor for adrenal
insufficiency, Cushing’s syndrome, and other corticosteroid-
associated toxicities.
Betamethasone, All PIs ↑ glucocorticoids expected Do not coadminister. Coadministration can result in adrenal
Methylpred- insufficiency and Cushing’s syndrome.
nisolone,
Triamcinolone
Local injections,
including intra-
articular, epidural, or
intra-orbital
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir ATV/c, ATV/r ↑ daclatasvir Decrease daclatasvir dose to 30 mg once daily.
ATV ↔ daclatasvir No dose adjustment necessary.
(unboosted),
DRV/c, DRV/r,
LPV/r
TPV/r No data No dosing recommendations available at this time.
Dasabuvir plus ATV ↔ ATV ATV 300 mg alone, without COBI or additional RTV, should be
Paritaprevir/ (unboosted) given in the morning with dasabuvir plus paritaprevir/ombitasvir/
Ombitasvir/RTV RTV.
DRV DRV Cmin ↓ 43% to 48% Do not coadminister.
LPV/r Paritaprevir AUC ↑ 117% Do not coadminister.
ATV/c, DRV/c, No data Do not coadminister.
TPV/r

Effect on PI and/
Concomitant
Drug
Concentrations
Hepatitis C Direct-Acting Antiviral Agents, continued
Elbasvir/ ATV/r Elbasvir AUC ↑ 4.8-fold Contraindicated.
Grazoprevir
Grazoprevir AUC ↑ 10.6-fold May increase the risk of ALT elevations due to a significant
ATV ↔ by elbasvir increase in grazoprevir plasma concentrations caused by
OATP1B1/3 inhibition.
ATV AUC ↑ 43% by grazoprevir
DRV/r Elbasvir AUC ↑ 66%
Grazoprevir AUC ↑ 7.5-fold
↔ DRV
LPV/r Elbasvir AUC ↑ 3.7-fold
Grazoprevir AUC ↑ 12.9-fold
↔ LPV
ATV ↑ grazoprevir expected
(unboosted),
ATV/c, DRV/c,
TPV/r
Glecaprevir/ ATV When Given with ATV/r 300/100 Contraindicated.
Pibrentasvir (unboosted), mg Once Daily:
ATV/c, ATV/r • Glecaprevir AUC ↑ 6.5-fold
• Pibrentasvir AUC ↑ 64%
DRV/c, DRV/r When Given with DRV/r 800/100 Do not coadminister.
mg Once Daily:
• Glecaprevir AUC ↑ 5-fold
• ↔ pibrentasvir
LPV/r Glecaprevir AUC ↑ 4-fold Do not coadminister.
Pibrentasvir ↑ 2.5-fold
TPV/r ↑ glecaprevir and pibrentasvir Do not coadminister.
expected
Ledipasvir/ ATV/r ATV AUC ↑ 33% No dose adjustment necessary.
Sofosbuvir
Ledipasvir AUC ↑ 113% Coadministration of ledipasvir/sofosbuvir with TDF and a
PI/r results in increased exposure to TDF. The safety of the
↔ sofosbuvir increased TDF exposure has not been established. Consider
DRV/r ↔ DRV expected alternative HCV or ARV drugs to avoid increased TDF toxicities.
If coadministration is necessary, monitor for TDF-associated
↔ ledipasvir/sofosbuvir adverse reactions.
ATV ↔ expected
(unboosted),
ATV/c, DRV/c,
LPV/r
TPV/r ↓ ledipasvir and sofosbuvir Do not coadminister.
expected

Effect on PI and/
Concomitant
Drug
Concentrations
Simeprevir All PIs Compared with Simeprevir 150 Do not coadminister.
mg Alone, Simeprevir 50 mg
plus DRV/r 800 mg/100 mg
Daily:
• Simeprevir AUC ↑ 159%
RTV 100 mg BID ↑ simeprevir

AUC 618%
Sofosbuvir TPV/r ↓ sofosbuvir expected Do not coadminister.
Sofosbuvir/ ATV/r ↔ ATV/r No dose adjustment necessary.
Velpatasvir
↔ sofosbuvir
Velpatasvir AUC ↑ 2.4-fold
DRV/r ↔ DRV/r No dose adjustment necessary.
Sofosbuvir AUC ↓ 28%
↔ velpatasvir
ATV ↔ sofosbuvir and velpatasvir No dose adjustment necessary.
(unboosted), expected
ATV/c, DRV/c,
LPV/r
TPV/r ↓ sofosbuvir expected Do not coadminister.
↓ velpatasvir expected
Sofosbuvir/ ATV When Given with ATV/r: Do not coadminister.
Velpatasvir/ (unboosted), • Voxilaprevir AUC ↑ 4.3-fold
Voxilaprevir ATV/c, ATV/r
• Velpatasvir AUC ↑ 93%
• Sofosbuvir AUC ↑ 40%
LPV/r ↑ voxilaprevir expected Do not coadminister.
DRV/c , DRV/r When Given with DRV/r: No dose adjustment needed.
• Voxilaprevir AUC ↑ 2.4-fold
• ↔ DRV/r, velpatasvir, and
sofosbuvir
TPV/r ↓ sofosbuvir expected Do not coadminister.
Effect on voxilaprevir is
unknown.
Herbal Products
St. John’s Wort All PIs ↓ PI expected Contraindicated.

Effect on PI and/
Concomitant
Drug
Concentrations
Hormonal Therapies
Hormonal ATV Ethinyl estradiol AUC ↑ 48% Prescribe oral contraceptive that contains no more than 30 mcg of
Contraceptives (unboosted) ethinyl estradiolb or recommend alternative contraceptive method.
Oral Norethindrone AUC ↑ 110%
Oral contraceptives containing less than 25 mcg of ethinyl
estradiol or progestins other than norethindrone or norgestimate
have not been studied.
ATV/r Ethinyl estradiol AUC ↓ 19% and Oral contraceptive should contain at least 35 mcg of ethinyl
Cmin ↓ 37% estradiol.c
Norgestimate ↑ 85% Oral contraceptives containing progestins other than
norethindrone or norgestimate have not been studied.
Norethindrone AUC ↑ 51% and
Cmin ↑ 67%
ATV/c Drospirenone AUC ↑ 2.3-fold Contraindicated with drospirenone-containing hormonal
contraceptive due to potential for hyperkalemia. Consider
Ethinyl estradiol AUC ↓ 22% alternative or additional contraceptive method or alternative ARV
drug.
DRV/c Drospirenone AUC ↑ 1.6-fold Clinical monitoring is recommended due to the potential for
hyperkalemia. Consider alternative or additional contraceptive
Ethinyl estradiol AUC ↓ 30% method or alternative ARV.
DRV/r, LPV/r, Ethinyl estradiol AUC ↓ 37% to Consider alternative or additional contraceptive method or
TPV/r 55% alternative ARV drug.
Norethindrone AUC ↓ 14% to
34%
With TPV/r:
• ↔ norethindrone AUC
Depot MPA LPV/r MPA AUC ↑ 46% No dose adjustment necessary.
Injectable
No significant change in Cmin
Etonogestrel- LPV/r Etonogestrel AUC ↑ 52% and Use standard dose.
Releasing Cmin ↑ 34%
Subdermal Implant All other PIs No data Consider alternative or additional contraceptive method or
alternative ARV drug.
Etonogestrel/ ATV/r Ethinyl estradiol AUC ↓ 26% Use standard dose.
Ethinyl Estradiol
Vaginal Ring Etonogestrel AUC ↑ 79%
Transdermal LPV/r ↔ LPV Use standard dose.
Ethinyl Estradiol/
Norelgestromin Ethinyl estradiol AUC ↓ 45%,
norelgestromin AUC ↑ 83%
All other PIs No data Consider alternative or additional contraceptive method or
alternative ARV drug.

Effect on PI and/
Concomitant
Drug
Concentrations
Hormonal Therapies, continued
Menopausal All PIs ↓ estrogen possible with Adjust estrogen dosage as needed based on clinical effects.
Hormone estradiol or conjugated estrogen
Replacement (equine and synthetic)
Therapy (HRT) All PIs ↑ drospirenone possible Adjust progestin/progesterone dosage as needed based on
clinical effects. Because drospirenone is prescribed as a lower
↑ medroxyprogesterone
dose for menopausal HRT than the products used for hormonal
↑ micronized progesterone contraceptives, it is not contraindicated with ATV/c products.
See Hormonal Contraceptives
for other progestin-PI
interactions
Gender-Affirming All PIs ↓ estradiol possible Adjust estradiol dosage as needed based on clinical effects and
Hormone Therapy endogenous hormone concentrations.
All PIs ↔ finasteride, goserelin, No dose adjustment necessary.
leuprolide acetate, and
spironolactone expected
All PIs ↑ dutasteride possible Adjust dutasteride dosage as needed based on clinical effects
and endogenous hormone concentrations.
All PIs ↓ testosterone possible Adjust testosterone dosage as needed based on clinical effects
and endogenous hormone concentrations.
HMG-CoA Reductase Inhibitors
Atorvastatin ATV ↑ atorvastatin possible Titrate atorvastatin dose carefully and use lowest dose necessary
(unboosted), while monitoring for toxicities.
ATV/r
ATV/c Atorvastatin AUC ↑ 9.2-fold, Cmax Coadministration is not recommended.
↑ 18.9-fold
DRV/r DRV/r plus atorvastatin 10 mg Titrate atorvastatin dose carefully and use the lowest dose
similar to atorvastatin 40 mg necessary while monitoring for toxicities. Do not exceed 20 mg
administered alone atorvastatin daily.
DRV/c Atorvastatin AUC ↑ 3.9-fold, Cmax Titrate atorvastatin dose carefully and use lowest dose necessary
↑ 4.2-fold while monitoring for toxicities. Do not exceed 20 mg atorvastatin
daily.
LPV/r Atorvastatin AUC ↑ 5.9-fold, Cmax Titrate atorvastatin dose carefully and use lowest dose necessary
↑ 4.7-fold while monitoring for toxicities. Do not exceed 20 mg atorvastatin
daily.
TPV/r Atorvastatin AUC ↑ 9.4-fold, Cmax Do not coadminister.
↑ 8.6-fold
Lovastatin All PIs Significant ↑ lovastatin expected Contraindicated.
Pitavastatin All PIs ATV ↑ pitavastatin AUC 31% No dose adjustment necessary.
and Cmax ↑ 60%
↔ ATV
DRV/r ↓ pitavastatin AUC 26%
↔ DRV/r
LPV/r ↓ pitavastatin AUC 20%
↔ LPV

Effect on PI and/
Concomitant
Drug
Concentrations
HMG-CoA Reductase Inhibitors, continued
Pravastatin ATV/c, ATV/r No data Titrate pravastatin dose carefully while monitoring for toxicities.
DRV/c, DRV/r With DRV/r: Titrate pravastatin dose carefully while monitoring for toxicities.
• Pravastatin AUC ↑ 81%
following single dose of
pravastatin
• Pravastatin AUC ↑ 23% at
steady state
LPV/r Pravastatin AUC ↑ 33% No dose adjustment necessary.
Rosuvastatin ATV/r Rosuvastatin AUC ↑ 3-fold, Cmax Titrate rosuvastatin dose carefully and use lowest dose necessary
↑ 7-fold while monitoring for toxicities. Do not exceed rosuvastatin 10 mg
ATV/c Rosuvastatin AUC ↑ 3.4-fold, daily.
Cmax ↑ 10.6-fold
DRV/c Rosuvastatin AUC ↑ 1.9-fold, Titrate rosuvastatin dose carefully and use the lowest dose
Cmax ↑ 3.8-fold necessary while monitoring for toxicities. Do not exceed
rosuvastatin 20 mg daily.
DRV/r Rosuvastatin AUC ↑ 48%, Cmax Titrate rosuvastatin dose carefully and use the lowest necessary
↑ 2.4-fold dose while monitoring for toxicities.
LPV/r Rosuvastatin AUC ↑ 2.1-fold, Titrate rosuvastatin dose carefully and use the lowest necessary
Cmax ↑ 4.7-fold dose. Do not exceed rosuvastatin 10 mg daily.
TPV/r Rosuvastatin AUC ↑ 26%, Cmax No dose adjustment necessary.
↑ 2.2-fold
Simvastatin All PIs Significant ↑ simvastatin Contraindicated.
expected
Immunosuppressants
Cyclosporine, All PIs ↑ immunosuppressant expected Initiate with an adjusted dose of immunosuppressant to account
Everolimus, for potential increased concentrations of the immunosuppressant
Sirolimus, and monitor for toxicities. Therapeutic drug monitoring of
Tacrolimus immunosuppressant is recommended. Consult with specialist as
necessary.

Effect on PI and/
Concomitant
Drug
Concentrations
Narcotics and Treatment for Opioid Dependence
Buprenorphine ATV Buprenorphine AUC ↑ 93% Do not coadminister.
Sublingual, buccal, (unboosted)
or implant Norbuprenorphined AUC ↑ 76%
↓ ATV possible
ATV/r Buprenorphine AUC ↑ 66% Monitor for sedation and other signs or symptoms of over-
medication. Buprenorphine dose reduction may be necessary. It
Norbuprenorphined AUC ↑ 105% may be necessary to remove implant and treat with a formulation
that permits dose adjustments.
DRV/r No significant effect on No dose adjustment necessary. Clinical monitoring is
buprenorphine recommended. When transferring buprenorphine from
transmucosal delivery to implantation, monitor to ensure
Norbuprenorphined AUC ↑ 46% buprenorphine effect is adequate and not excessive.
and Cmin ↑ 71%
LPV/r No significant effect
TPV/r No significant effect on Consider monitoring TPV level. When transferring buprenorphine
buprenorphine from transmucosal delivery to implantation, monitor to ensure
buprenorphine effect is adequate and not excessive.
Norbuprenorphined AUC, Cmax,
and Cmin ↓ 80%
TPV Cmin ↓ 19% to 40%
PI/c Effects unknown Titrate buprenorphine dose using the lowest initial dose.
Dose adjustment of buprenorphine may be needed. It may be
necessary to remove implant and treat with a formulation that
permits dose adjustments. Clinical monitoring is recommended.
Fentanyl All PIs ↑ fentanyl possible Clinical monitoring is recommended, including for potentially fatal
respiratory depression.
Methadone ATV No significant effect No dose adjustment necessary.
(unboosted)
PI/c Effects unknown Titrate methadone dose using the lowest feasible initial dose.
Dose adjustment of methadone may be needed. Clinical
monitoring is recommended.
All PI/r ATV/r and DRV/r ↓ Opioid withdrawal is unlikely but may occur. Dosage adjustment
R-methadonee AUC 16% to 18% of methadone is not usually required, but monitor for opioid
withdrawal and increase methadone dose as clinically indicated.
LPV/r ↓ methadone AUC 26%
to 53%
TPV/r ↓ R-methadonee AUC
48%
Oxycodone All PIs Oxycodone AUC ↑ 2.6-fold with Monitor for opioid-related adverse effects. Oxycodone dose
LPV/r reduction may be necessary.
Tramadol All PIs ↑ tramadol possible Tramadol dose reduction may be necessary. Monitor for tramadol
toxicities and clinical response.

Effect on PI and/
Concomitant
Drug
Concentrations
PDE5 Inhibitors
Avanafil All PIs except RTV (600 mg BID for 5 days) ↑ Coadministration is not recommended.
unboosted ATV avanafil AUC 13-fold and ↑ Cmax
2.4-fold
ATV No data Avanafil dose should not exceed 50 mg once every 24 hours.
(unboosted)
Sildenafil All PIs DRV/r plus sildenafil 25 mg For Treatment of Erectile Dysfunction:
similar to sildenafil 100 mg alone • Start with sildenafil 25 mg every 48 hours and monitor for
RTV 500 mg BID ↑ sildenafil adverse effects of sildenafil.
AUC 1,000% For Treatment of PAH:
• Contraindicated.
Tadalafil All PIs RTV 200 mg BID ↑ tadalafil AUC For Treatment of Erectile Dysfunction:
124% • Start with tadalafil 5-mg dose and do not exceed a single dose
TPV/r (1st dose) ↑ tadalafil AUC of tadalafil 10 mg every 72 hours. Monitor for adverse effects of
133% tadalafil.
No significant effect on TPV/r For Treatment of PAH

steady state In Patients on a PI >7 Days:
• Start with tadalafil 20 mg once daily and increase to tadalafil 40
mg once daily based on tolerability.
In Patients on Tadalafil who Require a PI:
• Stop tadalafil ≥24 hours before PI initiation. Seven days after
PI initiation, restart tadalafil at 20 mg once daily and increase to
tadalafil 40 mg once daily based on tolerability.
In Patients Switching between COBI and RTV:
• Maintain tadalafil dose.
For Treatment of Benign Prostatic Hyperplasia:
• Maximum recommended daily dose is tadalafil 2.5 mg per day.
Vardenafil All PIs RTV 600 mg BID ↑ vardenafil Start with vardenafil 2.5 mg every 72 hours and monitor for
AUC 49-fold adverse effects of vardenafil.
Sedative/Hypnotics
Alprazolam, All PIs ↑ benzodiazepine possible Consider alternative benzodiazepines, such as lorazepam,
Clonazepam, oxazepam, or temazepam.
Diazepam RTV (200 mg BID for 2 days) ↑
alprazolam half-life 222% and ↑
AUC 248%
Lorazepam, All PIs No data These benzodiazepines are metabolized via non-CYP450
Oxazepam, pathways; thus, there is less interaction potential than with other
Temazepam benzodiazepines.
Midazolam All PIs ↑ midazolam expected Oral midazolam is contraindicated with PIs.
Parenteral midazolam can be used with caution when given as a
single dose in a monitored situation for procedural sedation.
Suvorexant All PIs ↑ suvorexant expected Coadministration is not recommended.

Effect on PI and/
Concomitant
Drug
Concentrations
Sedative/Hypnotics, continued
Triazolam All PIs ↑ triazolam expected Contraindicated.
RTV (200 mg BID) ↑ triazolam
half-life 1,200% and AUC
2,000%
Zolpidem PI/c, PI/r ↑ zolpidem possible Initiate zolpidem at a low dose. Dose reduction may be
necessary.
Miscellaneous Drugs
Calcifediol All PIs ↑ calcifediol possible Dose adjustment of calcifediol may be required, and serum
25-hydroxyvitamin D, intact PTH, and serum calcium
concentrations should be closely monitored.
Cisapride All PIs ↑ cisapride expected Contraindicated.
Colchicine All PIs RTV 100 mg BID ↑ colchicine For Treatment of Gout Flares:
AUC 296% and Cmax 184% • Administer a single dose of colchicine 0.6 mg, followed by
Significant ↑ colchicine expected colchicine 0.3 mg 1 hour later. Do not repeat dose for at least 3
with all PIs, with or without COBI days.
or RTV For Prophylaxis of Gout Flares:
• Administer colchicine 0.3 mg once daily or every other day.
For Treatment of Familial Mediterranean Fever:
• Do not exceed colchicine 0.6 mg once daily or colchicine 0.3 mg
BID.
Do not coadminister in patients with hepatic or renal
impairment.
Dronabinol All PIs ↑ dronabinol possible Monitor for increased dronabinol-related adverse reactions.
Eluxadoline All PIs ↑ eluxadoline expected Administer eluxadoline at a dose of 75 mg twice daily and monitor
for eluxadoline-related adverse effects.
Enzalutamide All PIs ↓ PI expected Contraindicated.
Ergot Derivatives All PIs ↑ dihydroergotamine, Contraindicated.
ergotamine, methylergonovine
expected
Flibanserin All PIs ↑ flibanserin expected Contraindicated.
Irinotecan ATV ↑ irinotecan expected Contraindicated.
(unboosted),
ATV/c, ATV/r
Mitotane All PIs ↓ PI expected Contraindicated.
Salmeterol All PIs ↑ salmeterol possible Do not coadminister because of potential increased risk of
salmeterol-associated CV events.

a
DHA is an active metabolite of artemether.
b
he following products contain no more than 30 mcg of ethinyl estradiol combined with norethindrone or norgestimate (generic
T
formulations may also be available): Lo Minastrin Fe; Lo Loestrin Fe; Loestrin 1/20, 1.5/30; Loestrin Fe 1/20, 1.5/30; Loestrin 24 Fe;
Minastrin 24 Fe; Ortho Tri-Cyclen Lo.
c
he following products contain at least 35 mcg of ethinyl estradiol combined with norethindrone or norgestimate (generic formulations
T
may also be available): Brevicon; Femcon Fe; Modicon; Norinyl 1/35; Ortho-Cyclen; Ortho-Novum 1/35, 7/7/7; Ortho Tri-Cyclen; Ovcon
35; Tri-Norinyl.
d
Norbuprenorphine is an active metabolite of buprenorphine.
e
R-methadone is the active form of methadone.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: 17-BMP = beclomethasone 17-monopropionate; ALT = alanine aminotransferase; ART = antiretroviral therapy; ARV
= antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BID = twice
daily; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CNS = central nervous system; COBI = cobicistat;
CrCl = creatinine clearance; CV = cardiovascular; CYP = cytochrome P; DHA = dihydroartemisinin; DRV = darunavir; DRV/c = darunavir/
cobicistat; DRV/r = darunavir/ritonavir; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; FPV = fosamprenavir;
HCV = hepatitis C virus; HRT = hormone replacement therapy; IDV = indinavir; INR = international normalized ratio; LPV = lopinavir;
LPV/r = lopinavir/ritonavir; MPA = medroxyprogesterone acetate; NFV = nelfinavir; OATP = organic anion-transporting polypeptide; PAH
= pulmonary arterial hypertension; PDE5 = Phosphodiesterase Type 5; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r =
protease inhibitor/ritonavir; PK = pharmacokinetic; PPI = proton pump inhibitor; PTH = parathyroid hormone; QTc = QT corrected for heart
rate; RTV = ritonavir; SQV = saquinavir; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; TPV/r = tipranavir/ritonavir

Table 19b. Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Other
Drugs (Last updated October 25, 2018; last reviewed October 25, 2018) (page 1 of 10)
This table provides information relating to PK interactions between NNRTIs and non-ARV drugs. For
interactions between ARV agents and for dosing recommendations, refer to Tables 19c, 20a, and 20b.
drug is being initiated in a patient on a stable concomitant medication or if a new concomitant medication is
being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are
Note: DLV is not included in this table. Please refer to the DLV FDA package insert for information
regarding drug interactions. The term “All NNRTIs” in this table refers to all NNRTIs except for DLV.
Concomitant Effect on NNRTI and/

Drug Class/ NNRTIa or Concomitant Drug Dosing Recommendations and Clinical Comments
Name Concentrations
Acid Reducers
Antacids RPV ↓ RPV expected when given Give antacids at least 2 hours before or at least 4 hours
simultaneously after RPV.
H2 Receptor RPV ↓ RPV Give H2 receptor antagonists at least 12 hours before or
Antagonists at least 4 hours after RPV.
PPIs RPV With Omeprazole 20 mg Daily: Contraindicated. Do not coadminister.
• RPV AUC ↓ 40% and Cmin ↓ 33%
Alfuzosin, EFV, ETR, NVP ↓ alpha antagonist expected Consider alternative therapy. If coadministration is
Doxazosin, necessary, monitor for therapeutic effectiveness of alpha
Silodosin antagonist.
Tamsulosin EFV, ETR, NVP ↓ tamsulosin expected Monitor for therapeutic effectiveness of tamsulosin after 2
to 4 weeks of dosing. May need to increase to tamsulosin
0.8 mg once daily for patients who fail to respond to the
0.4 mg dose.
Anticoagulants/Antiplatelets
Apixaban EFV, ETR, NVP ↓ apixaban possible Consider alternative therapy.
Betrixaban All NNRTIs ↔ betrixaban expected No dose adjustment necessary.
Clopidogrel EFV, ETR ↓ activation of clopidogrel possible ETR may prevent metabolism of clopidogrel (inactive) to
its active metabolite. Avoid coadministration, if possible.
DOR, NVP, RPV ↔ clopidogrel expected No dose adjustment necessary.
Dabigatran All NNRTIs ↔ dabigatran expected No dose adjustment necessary.
Edoxaban All NNRTIs ↔ edoxaban expected No dose adjustment necessary.
Prasugrel All NNRTIs ↔ prasugrel expected No dose adjustment necessary.
Rivaroxaban EFV, ETR, NVP ↓ rivaroxaban possible Consider alternative therapy.
Ticagrelor EFV, ETR, NVP ↓ ticagrelor expected Consider alternative therapy.
Warfarin EFV, ETR, NVP ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose accordingly.

Name Concentrations
Anticonvulsants
Carbamazepine, EFV Carbamazepine plus EFV: Monitor anticonvulsant and EFV concentrations or, if
Phenobarbital, • Carbamazepine AUC ↓ 27% possible, use alternative anticonvulsant to those listed.
Phenytoin
• EFV AUC ↓ 36%
Phenytoin plus EFV:
• ↓ EFV
• ↓ phenytoin possible
ETR ↓ anticonvulsant and ETR possible Do not coadminister. Consider alternative anticonvulsant.
NVP ↓ anticonvulsant and NVP possible Monitor anticonvulsant and NVP concentrations and
virologic responses or consider alternative anticonvulsant.
DOR, RPV ↓ NNRTI possible Contraindicated. Do not coadminister. Consider
alternative anticonvulsant.
Eslicarbazepine All NNRTIs ↓ NNRTI possible Monitor virologic outcomes and consider monitoring
plasma concentrations of ARVs, or consider alternative
anticonvulsant or ARV drug.
Oxcarbazepine DOR, RPV ↓ NNRTI possible Contraindicated. Do not coadminister. Consider
alternative anticonvulsant.
Ethosuximide, ETR, EFV ↓ anticonvulsant possible Monitor seizure control and plasma concentrations of
Lacosamide, anticonvulsants (when available).
Tiagabine,
Zonisamide,
Lamotrigine EFV ↓ lamotrigine possible Monitor seizure control and plasma concentrations of
lamotrigine.
Antidepressants
Bupropion EFV, NVP Bupropion AUC ↓ 55% Titrate bupropion dose based on clinical response.
↓ bupropion possible
Citalopram, EFV, ETR, NVP ↓ antidepressant possible Titrate antidepressant dose based on clinical response.
Escitalopram
Fluoxetine, All NNRTIs ↔ antidepressant expected No dose adjustment necessary.
Fluvoxamine
Paroxetine EFV, ETR ↔ paroxetine observed with EFV No dose adjustment necessary.
or ETR
DOR, NVP, RPV ↔ expected with DOR, NVP or No dose adjustment necessary.
RPV
Nefazodone EFV, ETR, NVP ↓ nefazodone expected Monitor the antidepressant effect and titrate dose as
necessary. Monitor for ARV-related adverse events.
↑ NNRTI possible
DOR, RPV ↑ NNRTI possible Monitor for ARV-related adverse events.
Sertraline EFV Sertraline AUC ↓ 39% Titrate sertraline dose based on clinical response.
Trazodone EFV, ETR, NVP ↓ trazodone possible Monitor the therapeutic effect of trazodone and titrate
dose as necessary.

Name Concentrations
Antifungals
Fluconazole EFV ↔ fluconazole or EFV No dose adjustment necessary.
ETR ETR AUC ↑ 86% No dose adjustment necessary. Use with caution.
NVP NVP AUC ↑ 110% Increased risk of hepatotoxicity possible with this
combination. Monitor NVP toxicity or use alternative ARV
agent.
DOR,RPV ↑ NNRTI possible No dose adjustment necessary.
Isavuconazole EFV, ETR, NVP ↓ isavuconazole possible Dose adjustments for isavuconazole may be necessary.
Consider monitoring isavuconazole concentration and
antifungal response.
DOR, RPV ↑ NNRTI possible No dose adjustment necessary.
Itraconazole EFV Itraconazole and OH-itraconazole Failure to achieve therapeutic itraconazole concentrations
AUC, Cmax, and Cmin ↓ 35% to 44% has been reported. Avoid this combination if possible.
If coadministered, closely monitor itraconazole
concentration and adjust dose accordingly.
ETR ↓ itraconazole possible Dose adjustments for itraconazole may be necessary.
Monitor itraconazole level and antifungal response.
↑ ETR possible
NVP Itraconazole AUC ↓ 61% Avoid this combination if possible. If coadministered,
monitor itraconazole concentration and adjust dose
↑ NVP possible accordingly.
Posaconazole EFV Posaconazole AUC ↓ 50% Avoid concomitant use unless the benefit outweighs
the risk. If coadministered, monitor posaconazole
↔ EFV concentration and adjust dose accordingly.
DOR, ETR, NVP, ↑ NNRTI possible Monitor for NNRTI toxicities.
RPV
Voriconazole EFV Voriconazole AUC ↓ 77% Contraindicated at standard doses.
EFV AUC ↑ 44% Dose Adjustment:
• Voriconazole 400 mg BID, EFV 300 mg daily
ETR ↔ Voriconazole AUC No dose adjustment necessary.
ETR AUC ↑ 36%
NVP ↓ voriconazole possible Monitor for toxicity and antifungal response and/or
voriconazole concentration.
↑ NVP possible
Antihyperglycemics
Canagliflozin, All NNRTIs ↔ antihyperglycemic expected No dose adjustment necessary.
Dapagliflozin,
Empagliflozin,
Sitagliptin
Linagliptin, EFV, ETR, NVP ↓ antihyperglycemic possible Monitor glycemic control.
Saxagliptin

Name Concentrations
Antimalarials
Artemether/ EFV Artemether AUC ↓ 79% Consider alternative ARV or antimalarial drug. If used in
Lumefantrine combination, monitor closely for antimalarial efficacy.
DHA AUC ↓ 75%
Lumefantrine AUC ↓ 56%
ETR Artemether AUC ↓ 38% Clinical significance of the reduced antimalarial drug
concentrations unknown. If used in combination with
↔ DHA AUC
ETR, monitor for antimalarial efficacy.
↔ Lumefantrine AUC
↔ ETR AUC
NVP Artemether AUC ↓ 67% to 72% Clinical significance unknown. If used, monitor closely for
antimalarial efficacy and lumefantrine toxicity.
DHA:
• Study results are conflicting. DHA
AUC ↓ 37% in one study, no
difference in another.
Lumefantrine:
• Study results are conflicting.
Lumefantrine AUC ↓ 25% to 58%
in 2 studies but ↑ 56% in another.
Atovaquone/ EFV Atovaquone AUC ↓ 75% No dose recommendation. Consider alternative drug for
Proguanil malaria prophylaxis, if possible.
Proguanil AUC ↓ 43%
Antimycobacterials
Bedaquiline EFV, ETR ↓ bedaquiline possible Do not coadminister.
NVP ↔ bedaquiline AUC No dose adjustment necessary.
Clarithromycin EFV Clarithromycin AUC ↓ 39% Monitor for effectiveness or consider alternative agent,
such as azithromycin, for MAC prophylaxis and treatment.
ETR Clarithromycin AUC ↓ 39% Consider alternative agent, such as azithromycin, for
MAC prophylaxis and treatment.
ETR AUC ↑ 42%
NVP Clarithromycin AUC ↓ 31% Monitor for effectiveness or use alternative agent, such
as azithromycin, for MAC prophylaxis and treatment.
NVP AUC ↑ 26%
RPV ↔ clarithromycin expected Consider alternative macrolide, such as azithromycin, for
MAC prophylaxis and treatment.
↑ RPV possible
Rifabutin DOR DOR AUC ↓ 50% Increase DOR dose to 100 mg twice daily. No dose
adjustment for rifabutin.
EFV Rifabutin ↓ 38% Dose:
• Rifabutin 450–600 mg/day; or
• Rifabutin 600 mg 3 times/week if EFV is not
coadministered with a PI.
ETR ↔ Rifabutin and metabolite AUC Do not coadminister ETR plus PI/r with rifabutin.
ETR AUC ↓ 37% Use rifabutin 300 mg once daily if ETR is administered
without PI/r

Name Concentrations
Antimycobacterials, continued
Rifabutin, NVP Rifabutin AUC ↑ 17% and No dose adjustment necessary. Use with caution.
continued metabolite AUC ↑ 24%
NVP Cmin ↓ 16%
RPV Rifabutin plus RPV 50 mg Once Increase RPV dose to 50 mg once daily. No dose
Daily Compared to RPV 25 mg adjustment for rifabutin.
Once Daily Alone:
• ↔ RPV AUC and Cmin
Rifampin DOR DOR AUC ↓ 88% Contraindicated.
EFV EFV AUC ↓ 26% Do not use EFV 400 mg with rifampin. Maintain EFV
dose at 600 mg once daily and monitor for virologic
response.
ETR Significant ↓ ETR possible Do not coadminister.
NVP NVP ↓ 20% to 58% Do not coadminister.
RPV RPV AUC ↓ 80% Contraindicated.
Rifapentine EFV ↔ EFV concentrations No dose adjustment necessary.
ETR, NVP ↓ NNRTI possible Do not coadminister.
DOR, RPV ↓ NNRTI expected Contradindicated.
Antipneumocystis and Antitoxoplasmosis Drugs
Atovaquone EFV Atovaquone AUC ↓ 44% to 47% Consider alternative agent for PCP or toxoplasmosis
treatment or use alternative ARV drug.
If used in combination, monitor therapeutic efficacy of
atovaquone.
Antipsychotics
Aripiprazole EFV, ETR, NVP ↓ aripiprazole expected Monitor effectiveness of antipsychotic. Consider
doubling usual dose of aripiprazole over 1–2 weeks.
Refer to aripiprazole prescribing information for dosing
recommendations.
Brexpiprazole EFV, ETR, NVP ↓ brexpiprazole expected Monitor effectiveness of antipsychotic. Consider
doubling the usual dose of brexpiprazole and making
further adjustments based on clinical response. Refer to
brexpiprazole prescribing information.
Cariprazine EFV, ETR, NVP ↓ cariprazine and ↑ or ↓ active Coadministration is not recommended.
metabolite possible
Olanzapine EFV ↓ olanzapine possible Monitor effect of olanzapine.
DOR, ETR, NVP, ↔ olanzapine expected No dose adjustment necessary.
RPV
Pimozide EFV, ETR, NVP ↓ pimozide possible Monitor therapeutic effectiveness of pimozide
Lurasidone, EFV, ETR, NVP ↓ antipsychotic possible Monitor effect of antipsychotic.
Pimavanserin,
Quetiapine,
Thioridazine

Name Concentrations
Benzodiazepines
Alprazolam EFV, ETR, NVP ↓ alprazolam possible Monitor for therapeutic effectiveness of alprazolam.
Diazepam EFV, NVP ↓ diazepam possible Monitor for therapeutic effectiveness of diazepam.
ETR ↑ diazepam possible Decreased dose of diazepam may be necessary. Monitor
for diazepam toxicity.
Lorazepam EFV ↔ lorazepam AUC No dose adjustment necessary.
ETR, NVP ↔ lorazepam expected
Midazolam EFV ↑ or ↓ midazolam possible Monitor therapeutic effectiveness and toxicity of
midazolam.
ETR Midazolam AUC ↓ 31% Monitor therapeutic effectiveness of midazolam.
Midazolam active metabolite Cmax
↑ 57%
NVP ↓ midazolam possible Monitor therapeutic effectiveness of midazolam.
Triazolam EFV, ETR, NVP ↓ triazolam possible Monitor therapeutic effectiveness of triazolam.
Cardiac Medications
Dihydropyridine EFV, ETR, NVP ↓ CCBs possible Titrate CCB dose based on clinical response.
CCBs
Diltiazem, EFV Diltiazem AUC ↓ 69% Titrate diltiazem or verapamil dose based on clinical
Verapamil response.
↓ verapamil possible
ETR, NVP ↓ diltiazem or verapamil possible
Corticosteroids
Dexamethasone DOR, EFV, ETR, ↓ NNRTI possible Consider alternative corticosteroid for long-term use. If
NVP dexamethasone is used with NNRTI, monitor virologic
response.
RPV Significant ↓ RPV possible Contraindicated with more than a single dose of
dexamethasone.
Hepatitis C Direct-Acting Antiviral Agents
Daclatasvir EFV, ETR, NVP Daclatasvir 120 mg Once Daily The recommended dose is daclatasvir 90 mg once daily.
plus EFV 600 mg Daily Compared
with Daclatasvir 60 mg Alone:
• Daclatasvir Cmin ↓ 17%, AUC ↑
37%
DOR, RPV No data No dose adjustment necessary.
Dasabuvir plus DOR ↑ DOR possible No dose adjustment necessary.
Paritaprevir/ EFV No data Contraindicated.
Ombitasivir/RTV
ETR, NVP ↓ DAAs possible Do not coadminister.
RPV RPV AUC ↑ 150% to 225% Do not coadminister, due to potential for QT interval
prolongation with higher concentrations of RPV.

Name Concentrations
Elbasvir/ EFV Elbasvir AUC ↓ 54% Contraindicated.
Grazoprevir
Grazoprevir AUC ↓ 83%
EFV ↔ by grazoprevir
EFV ↔ AUC by elbasvir
ETR, NVP ↓ elbasvir and grazoprevir Do not coadminister.
expected
DOR, RPV ↔ Elbasvir, grazoprevir No dose adjustment necessary.
↔ DOR, RPV
Glecaprevir/ DOR ↑ DOR expected No dose adjustment necessary.
Pibrentasvir EFV ↓ glecaprevir and pibrentasvir Do not coadminister.
expected
ETR , NVP ↓ glecaprevir and pibrentasvir
possible
RPV ↔ glecaprevir, pibrentasvir No dose adjustment necessary.
RPV AUC ↑ 84%
Ledipasvir/ EFV Ledipasvir AUC, Cmin, and Cmax ↓ No dose adjustment necessary.
Sofosbuvir 34%
↔ sofosbuvir
ETR, NVP No significant effect expected
DOR, RPV ↔ Ledipasvir, sofosbuvir
↔ DOR, RPV
Simeprevir DOR No significant effect expected. No dose adjustment necessary.
EFV Simeprevir AUC ↓ 71%, Cmin ↓ Do not coadminister.
91%
↔ EFV
ETR, NVP ↓ simeprevir expected Do not coadminister.
RPV ↔ simeprevir and RPV No dose adjustment necessary.
Sofosbuvir/ EFV Velpatasvir AUC ↓ 43%, Cmax ↓ Do not coadminister.
Velpatasvir 37% and Cmin ↓ 47%
ETR, NVP ↓ velpatasvir expected Do not coadminister.
DOR, RPV No significant effect expected No dose adjustment necessary.
Sofosbuvir/ EFV Velpatasvir AUC ↓ 43% , Cmax ↓ Do not coadminister.
Velpatasvir/ 37%, and Cmin ↓ 47%
Voxilaprevir
↓ voxilaprevir expected
ETR, NVP ↓ voxilaprevir expected Do not coadminister.
DOR, RPV No signficant effect expected No dose adjustment necessary.

Name Concentrations
Herbal Products
St. John’s Wort EFV, ETR, NVP ↓ EFV, ETR, and NVP expected Do not coadminister.
DOR, RPV ↓ NNRTI expected Contraindicated.
Hormonal Therapies
Hormonal EFV ↔ Ethinyl estradiol Use alternative or additional contraceptive methods.
Contraceptives,
Oral Etonogestrel (metabolite of oral
desogestrel) Cmin ↓ 61%
Levonorgestrel (metabolite of oral
norgestimate) AUC ↓ 83%
Norelgestromin (metabolite of oral
norgestimate) AUC ↓ 64%
ETR Ethinyl estradiol AUC ↑ 22% No dose adjustment necessary.
No significant effect on
norethindrone
NVP Ethinyl estradiol AUC ↓ 29%, Cmin Based on clinical data demonstrating no change in
↓ 58% effectiveness, no dose adjustment necessary.
Norethindrone AUC ↓ 18%
Etonogestrel (metabolite of oral
desogestrel) Cmin ↓ 22%
RPV ↔ Ethinyl estradiol No dose adjustment necessary.
↔ Norethinodrone
DOR ↔ Ethinyl estradiol No dose adjustment necessary.
↔ Levonorgestrel
Depot Medroxy- EFV, NVP DMPA: no significant change No dose adjustment necessary.
progesterone
Acetate (MPA)
Injectable
Etonogestrel- EFV Etonogestrel AUC ↓ 63% to 82% Use alternative or additional contraceptive methods.
Releasing NVP Etonogestrel: no significant change No dose adjustment necessary.
Subdermal
Implant
Etonogestrel/ EFV Ethinyl estradiol (intravaginal ring) Use alternative or additional contraceptive methods.
Ethinyl Estradiol AUC ↓ 56%
Vaginal Ring
Etonogestrel (intravaginal ring)
AUC ↓ 81%
Levonorestrel- EFV Levonorgestrel AUC ↓ 47% Use alternative or additional contraceptive methods.
Releasing
Subdermal Unintended pregnancies were observed in women who
Implant used EFV and levonorgestrel implant concomitantly.
NVP Levonorgestrel AUC ↑ 35% No dose adjustment necessary.
Levonorgestrel EFV Levonorgestrel AUC ↓ 58% Effectiveness of emergency postcoital contraception may
For emergency be diminished.
contraception

Name Concentrations
Hormonal Therapies, continued
Menopausal EFV, ETR, NVP ↓ estrogen possible with estradiol Monitor menopausal symptoms. Titrate to the dose of
Hormone or conjugated estrogen (equine hormonal therapy that achieves menopausal symptom
Replacement and synthetic) relief.
Therapy
↓ medroxyprogesterone possible
↓ micronized progesterone
possible
↓ drospirenone possible
See Hormonal Contraceptives for
other progestin-NNRTI interactions
Gender-Affirming EFV, ETR, NVP ↓ estradiol possible Monitor feminizing effects of estrogen and antiandrogen
Hormone therapy and titrate dosing as necessary to achieve
Therapy ↔ goserelin, leuprolide acetate, therapeutic goals.
and spironolactone expected
↓ dutasteride and finasteride
possible
EFV, ETR, NVP ↓ testosterone possible Monitor masculinizing effects of testosterone and titrate
testosterone dose as necessary to achieve therapeutic
goals.
Atorvastatin EFV, ETR Atorvastatin AUC ↓ 32% to 43% Adjust atorvastatin dose according to lipid response, but
do not exceed the maximum recommended dose.
NVP ↓ atorvastatin possible Adjust atorvastatin dose according to lipid response, but
do not exceed the maximum recommended dose.
DOR, RPV ↔ atorvastatin AUC No dose adjustment necessary.
Fluvastatin EFV, ETR ↑ fluvastatin possible Dose adjustments for fluvastatin may be necessary.
Monitor for fluvastatin toxicity.
Lovastatin, EFV Simvastatin AUC ↓ 68% Adjust simvastatin dose according to lipid response, but
Simvastatin do not exceed the maximum recommended dose. If EFV
Simvastatin active metabolite AUC is used with a PI/r, simvastatin and lovastatin should be
↓ 60% avoided.
ETR, NVP ↓ lovastatin possible Adjust lovastatin or simvastatin dose according to
lipid responses but do not exceed the maximum
↓ simvastatin possible recommended dose. If ETR or NVP is used with a PI/r,
simvastatin and lovastatin should be avoided.
Pitavastatin EFV ↔ pitavastatin AUC No dose adjustment necessary.
DOR, ETR, NVP, ↔ pitavastatin expected No dose adjustment necessary.
RPV
Pravastatin EFV Pravastatin AUC ↓ 44% Adjust statin dose according to lipid responses, but do not
ETR ↓ pravastatin possible exceed the maximum recommended dose.
Rosuvastatin EFV, ETR, NVP ↔ rosuvastatin expected No dose adjustment necessary.

Name Concentrations
Immunosuppressants
Cyclosporine, EFV, ETR, NVP ↓ immunosuppressant possible Increase in immunosuppressant dose may be necessary.
Everolimus, Therapeutic drug monitoring of immunosuppressant is
Sirolimus, recommended. Consult with specialist as necessary.
Tacrolimus
Narcotics/Treatments for Opioid Dependence
Buprenorphine EFV Buprenorphine AUC ↓ 50% No dose adjustment recommended; monitor for
Sublingual or withdrawal symptoms.
Norbuprenorphineb AUC ↓ 71%
buccal
ETR Buprenorphine AUC ↓ 25% No dose adjustment necessary.
NVP No significant effect No dose adjustment necessary.
Buprenorphine EFV, ETR, NVP No data Clinical monitoring is recommended if NNRTI is initiated
Implant after insertion of buprenorphine implant.
Methadone EFV Methadone AUC ↓ 52% Opioid withdrawal common; increased methadone dose
often necessary.
DOR, ETR No significant effect No dose adjustment necessary.
NVP Methadone AUC ↓ 37% to 51% Opioid withdrawal is common; increased methadone
dose is often necessary.
No significant effect on NVP
RPV R-methadonec AUC ↓ 16% No dose adjustment necessary, but monitor for
withdrawal symptoms.
PDE5 Inhibitors
Sildenafil DOR, RPV ↔ sildenafil expected No dose adjustment necessary.
ETR Sildenafil AUC ↓ 57% May need to titrate sildenafil dose based on clinical effect.
EFV, NVP ↓ sildenafil possible
Tadalafil EFV, ETR, NVP ↓ tadalafil possible May need to titrate tadalafil dose based on clinical effect.
RPV ↔ tadalafil No dose adjustment necessary.
Avanafil, EFV, ETR, NVP ↓ PDE5 inhibitor possible May need to increase PDE5 inhibitor dose based on
Vardenafil clinical effect.
Miscellaneous Drugs
Enzalutamide All NNRTIs ↓ NNRTI expected Contraindicated.
Mitotane All NNRTIs ↓ NNRTI expected Contraindicated.
a
Approved dose for RPV is 25 mg once daily. Most PK interaction studies were performed using 75 mg to 150 mg per dose.
b
Norbuprenorphine is an active metabolite of buprenorphine.
c
R-methadone is the active form of methadone.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: ARV = antiretroviral; AUC = area under the curve; BID = twice daily; CCB = calcium channel blocker; Cmax = maximum
plasma concentration; Cmin = minimum plasma concentration; DAA = direct-acting antiviral; DHA = dihydroartemisinin; DMPA = depot
medroxyprogesterone acetate; DOR = doravirine; EFV = efavirenz; ETR = etravirine; HMG-CoA = hydroxy-methylglutaryl-coenzyme A; INR
= international normalized ratio; MAC = Mycobacterium avium complex; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP =
nevirapine; OH-itraconazole = active metabolite of itraconazole; PCP = Pneumocystis jirovecii pneumonia; PDE5 = phosphodiesterase type 5;
PI = protease inhibitor; PI/r = protease inhibitor/ritonavir; PK = pharmacokinetic; PPI = proton pump inhibitor; RPV = rilpivirine; RTV = ritonavir

Table 19c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs
(Including Antiretroviral Agents) (Last updated October 25, 2018; last reviewed October 25, 2018)
(page 1 of 3)
Recommendations for managing a particular drug interaction may differ depending on whether a new
ARV drug is being initiated in a patient on a stable concomitant medication or whether a new concomitant
medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug
interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed
concomitantly.
Note: Interactions associated with ddI and d4T are not included in this table. Please refer to FDA product
labels for information regarding interactions between ddI or d4T and other concomitant drugs.
Concomitant Drug Class/ Effect on NRTI and/or Concomitant Dosage Recommendations and Clinical
NRTI
Name Drug Concentrations Comments
Cytomegalovirus and Hepatitis B Antivirals
Adefovir TDF No data Do not coadminister. Serum concentrations of
TDF and/or other renally eliminated drugs may
increase.
Ganciclovir, TAF, TDF No data Serum concentrations of ganciclovir and/or TFV
Valganciclovir may increase. Monitor for dose-related toxicities.
ZDV No significant effect Potential increase in hematologic toxicities.
Hepatitis C Antiviral Agents
Glecaprevir/Pibrentasvir TAF, TDF No significant effect No dose adjustment necessary.
Ledipasvir/Sofosbuvir, TAF No significant effect No dose adjustment.
Sofosbuvir/Velpatasvir, TDF Ledipasvir ↑ TFV AUC 40% to 98% No dose adjustment necessary.
Sofosbuvir/Velpatasvir/ when TDF is given with RPV and EFV
Voxilaprevir The safety of increased TFV exposure when
Further ↑ TFV possible if TDF is given ledipasvir/sofosbuvir is coadministered with TDF
with PIs plus a PI/r or PI/c has not been established.
Consider alternative HCV or ARV drugs to avoid
increased TFV toxicities.
Consider using TAF in patients at risk of TDF-
associated adverse events. If TDF is used in these
patients, monitor for TDF toxicity.
Coadministration of ledipasvir/sofosbuvir with
EVG/c/TDF/FTC is not recommended.
Ribavirin TDF With Sofosbuvir 400 mg: No dose adjustment necessary.
• ↔ TFV AUC
ZDV Ribavirin inhibits phosphorylation of Avoid coadministration if possible, or closely
ZDV. monitor HIV virologic response and possible
hematologic toxicities.
INSTIs
DTG TAF ↔ TAF AUC No dose adjustment necessary.
TDF ↔ TDF AUC No dose adjustment necessary.
↔ DTG AUC
RAL TDF RAL AUC ↑ 49% No dose adjustment necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, No significant effect No dose adjustment necessary.
TDF, TAF,
ZDV

(page 2 of 3)
NRTI
Narcotics/Treatment for Opioid Dependence, continued
Methadone ABC Methadone clearance ↑ 22% No dose adjustment necessary.
ZDV ZDV AUC ↑ 29% to 43% Monitor for ZDV-related adverse effects.
Other
Atovaquone ZDV ZDV AUC ↑ 31% Monitor for ZDV-related adverse effects.
Anticonvulsants TAF With Carbamazepine: Coadministration is not recommended.
Carbamazepine, • TAF AUC ↓ 55%
oxcarbazepine,
phenobarbital, phenytoin ↓ TAF possible with other
anticonvulsants
Antimycobacterial TAF TAF AUC ↓ 55% Coadministration is not recommended.
Rrifampin
TFV-DP (intracellular active moiety)
AUC ↓ 36%
TAF plus Rifampin Compared with TDF
Alone:
• TFV-DP (intracellular active moiety)
AUC ↑ 4.2-fold
With Twice-Daily TAF 25 mg
Compared with Once-Daily TAF
without Rifampin:
• TAF AUC ↓ 14%
• TFV-DP (intracellular active moiety)
AUC ↓ 24%
TDF ↔ AUC TFV No dose adjustment necessary.
Rifabutin, Rifapentine TAF ↓ TAF possible Coadministration is not recommended.
St. John’s Wort TAF ↓ TAF possible Coadministration is not recommended.
PIs (HIV)
ATV (Unboosted), ATV/c, TAF TAF 10 mg with ATV/r: No dose adjustment (use TAF 25 mg).
ATV/r • TAF AUC ↑ 91%
TAF 10 mg with ATV/c:
• TAF AUC ↑ 75%
TDF With ATV (Unboosted): Avoid concomitant use without RTV or COBI.
• ATV AUC ↓ 25% and Cmin ↓ 23% Dose:
to 40% (higher Cmin with RTV than
without RTV) • ATV 300 mg daily plus (RTV 100 mg or COBI 150
mg) daily when coadministered with TDF 300 mg
TFV AUC ↑ 24% to 37% daily
• If using TDF and H2 receptor antagonist in an
ART-experienced patient, use ATV 400 mg daily
plus (RTV 100 mg or COBI 150 mg) daily
Monitor for TDF-associated toxicity.
ZDV With ATV (Unboosted): Clinical significance unknown.
• ZDV Cmin ↓ 30% and ↔ ZDV AUC

(page 3 of 3)
NRTI
PIs (HIV), continued
DRV/c TAF TAF 25 mg with DRV/c: No dose adjustment necessary.
• ↔ TAF
TDF ↑ TDF possible Monitor for TDF-associated toxicity.
DRV/r TAF TAF 10 mg with DRV/r: No dose adjustment necessary.
• ↔ TAF
TDF TFV AUC ↑ 22% and Cmin ↑ 37% Clinical significance unknown. Monitor for TDF-
associated toxicity.
LPV/r TAF TAF 10 mg with DRV/r: No dose adjustment necessary.
• TAF AUC ↑ 47%
TDF ↔ LPV/r AUC Clinical significance unknown. Monitor for TDF-
associated toxicity.
TFV AUC ↑ 32%
TPV/r ABC ABC AUC ↓ 35% to 44% Appropriate doses for this combination have not
been established.
TAF ↓ TAF expected Coadministration is not recommended.
TDF ↔ TDF AUC No dose adjustment necessary.
TPV AUC ↓ 9% to 18% and Cmin ↓ 12%
to 21%
ZDV ZDV AUC ↓ 31% to 42% Appropriate doses for this combination have not
been established.
↔ TPV AUC
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmin = minimum plasma concentration; COBI = cobicistat;
d4T = stavudine; ddI = didanosine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG
= elvitegravir; FDA = Food and Drug Administration; FTC = emtricitabine; HCV = hepatitis C virus; INSTI = integrase strand transfer
inhibitors; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = protease inhibitor/
cobicistat; PI/r = protease inhibitor/ritonavir; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TDF =
tenofovir disoproxil fumarate; TFV = tenofovir; TFV-DP = tenofovir diphosphate; TPV/r = tipranavir/ritonavir; ZDV = zidovudine

Table 19d. Drug Interactions Between Integrase Strand Transfer Inhibitors and Other Drugs (Last
updated October 25, 2018; last reviewed October 25, 2018) (page 1 of 15)
This table provides information on known or predicted PK interactions between INSTIs (BIC, DTG, EVG,
or RAL) and non-ARV drugs. EVG is always coadministered with COBI. Recommendations for managing a
particular drug interaction may differ depending on whether a new ARV drug is being initiated in a patient on
a stable concomitant medication or whether a new concomitant medication is being initiated in a patient on a
stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several
drugs with competing metabolic pathways are prescribed concomitantly.
Concomitant Drug Effect on INSTI or Concomitant Drug Dosing Recommendations and Clinical
INSTI
Class/Name Concentrations Comments
Alfuzosin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ alfuzosin expected Contraindicated.
Doxazosin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ doxazosin possible Initiate doxazosin at lowest dose and titrate
while monitoring for clinical response/toxicity.
Dose reduction may be necessary.
Tamsulosin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ tamsulosin expected Coadministration is not recommended.
If coadministered, monitor for tamsulosin
toxicities.
Terazosin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ terazosin possible Initiate terazosin at lowest dose and titrate while
monitoring for clinical response/toxicity. Dose
reduction may be necessary.
Silodosin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ silodosin expected Contraindicated.
Acid Reducers
Al, Mg, BIC ↔ BIC AUC if antacid is given 2 hours after With Antacids Containing Al/Mg or Ca:
+/- BIC and under fasting conditions • BIC can be taken under fasting conditions at
Ca-Containing least 2 hours before antacids containing Al/
Antacids BIC AUC ↓ 79% if given simultaneously with
antacid Mg or Ca.
Please refer to the
Miscellaneous Drugs BIC AUC ↓ 52% if antacid is given 2 hours Do not coadminister BIC simultaneously with, or
section of this table before BIC 2 hours after, antacids containing Al/Mg or Ca.
for recommendations DTG DTG AUC ↓ 74% if given simultaneously with Give DTG at least 2 hours before or at least
on use with other antacid 6 hours after antacids containing polyvalent
polyvalent cation cations.
products (e.g., Fe, DTG AUC ↓ 26% if given 2 hours before
Ca supplements, antacid
multivitamins). EVG/c EVG AUC ↓ 40% to 50% if given Separate EVG/c/TDF/FTC and antacid
simultaneously with antacid administration by >2 hours.
EVG AUC ↓ 15% to 20% if given 2 hours
before or after antacid; ↔ with 4-hour interval

INSTI
Acid Reducers, continued
Al, Mg, RAL Al/Mg Hydroxide Antacid: Do not coadminister RAL and Al-Mg
+/- • RAL Cmin ↓ 49% to 63% hydroxide antacids. Use alternative acid
Ca-Containing reducing agent.
Antacids, continued CaCO3 Antacid:
With CaCO3 Antacids:
Please refer to the • RAL (400 mg BID) Cmin ↓ 32%
Miscellaneous Drugs • RAL 1200 mg once daily: Do not
• RAL (1200 mg once daily) Cmin ↓ 48% to 57% coadminister.
section of this table
for recommendations • RAL 400 mg BID: No dose adjustment or
on use with other separation necessary.
polyvalent cation
products (e.g., Fe,
Ca supplements,
multivitamins).
H2-Receptor BIC, DTG, No significant effect No dose adjustment necessary.
Antagonists EVG/c
RAL RAL AUC ↑ 44% and Cmax ↑ 60% No dose adjustment necessary.
PPIs BIC, DTG, No significant effect No dose adjustment necessary.
EVG/c
RAL RAL AUC ↑ 37% and Cmin ↑ 24% No dose adjustment necessary.
Anticoagulants and Antiplatelets
Apixaban BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ apixaban expected In Patients Requiring Apixaban 2.5 mg Twice
Daily:
• Coadministration is not recommended.
In Patients Requiring Apixaban 5 mg or 10 mg
Twice Daily:
• Reduce apixaban dose by 50%.
Betrixaban BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ betrixaban expected Administer initial single dose of betrixaban 80
mg, followed by betrixaban 40 mg once daily.
Dabigatran BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ dabigatran expected Dabigatran dosing recommendation depends
on indication and renal function. Refer to
Dabigatran AUC ↑ 110% to 127% with COBI dabigatran prescribing information for dosing
150 mg alone instruction when used with P-gp inhibitors.
Edoxaban BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↔ or ↑ edoxaban expected For Stroke Prevention in Nonvalvular Atrial
Fibrillation:
• No dose adjustment necessary.
For Deep Venous Thrombosis and Pulmonary
Embolism:
• Administer edoxaban 30 mg once daily.
Rivaroxaban BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ rivaroxaban expected Coadministration is not recommended.

INSTI
Anticoagulants and Antiplatelets, continued
Ticagrelor BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ ticagrelor expected Coadministration is not recommended.
Vorapaxar BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ vorapaxar expected Coadministration is not recommended.
Warfarin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ or ↓ warfarin possible Monitor INR and adjust warfarin dose
accordingly.
Anticonvulsants
Carbamazepine BIC ↓ BIC possible Consider using an alternative anticonvulsant or
ARV.
DTG DTG AUC ↓ 49% Increase DTG dose to 50 mg BID in treatment-
naive or treatment-experienced, INSTI-naive
patients.
Use alternative anticonvulsant for INSTI-
experienced patients with known or suspected
INSTI resistance.
EVG/c Carbamazepine AUC ↑ 43% Contraindicated.
EVG AUC ↓ 69% and Cmin ↓ >99%
↓ COBI expected
RAL ↓ or ↔ RAL possible Coadministration is not recommended.
Eslicarbazepine All INSTIs ↓ INSTI possible Consider using an alternative anticonvulsant or
ARV.
↓ COBI possible
Ethosuximide BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ ethosuximide possible Clinically monitor for ethosuximide toxicities.
Lamotrigine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c No data Monitor anticonvulsant level and adjust dose
accordingly.
Oxcarbazepine All INSTIs ↓ INSTI possible Consider using an alternative anticonvulsant or
ARV.
↓ COBI possible
Phenobarbital BIC ↓ BIC possible Coadministration is not recommended.
Phenytoin DTG ↓ DTG possible Coadministration is not recommended.
EVG/c ↓ EVG/c expected Contraindicated.
RAL ↓ or ↔ RAL possible Coadministration is not recommended.
Valproic Acid All INSTIs No data Monitor valproic acid concentration and
virologic response.

INSTI
Antidepressants/Anxiolytics/Antipsychotics
Also see Sedative/Hypnotics section below.
Aripiprazole BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ aripiprazole expected Administer 25% of the usual aripiprazole dose.
Titrate based on clinical monitoring for efficacy
and toxicity. Refer to aripiprazole label for
dosing recommendations in patients who are
known to be CYP2D6 poor metabolizers or who
have major depressive disorder.
Brexpiprazole BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ brexpiprazole expected Administer 25% of the usual brexpiprazole
dose. Titrate based on clinical monitoring for
efficacy/toxicity. Refer to brexpiprazole label for
dosing recommendations in patients who are
known to be CYP2D6 poor metabolizers or who
have major depressive disorder.
Bupropion BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ bupropion possible Titrate bupropion dose based on clinical
response.
Buspirone BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ buspirone possible Initiate buspirone at a low dose. Dose reduction
may be necessary.
Cariprazine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ cariprazine expected Starting Cariprazine in a Patient Already on
EVG/c:
• Administer cariprazine 1.5 mg on Day 1 and
Day 3, with no dose given on Day 2.
• From Day 4 onward, administer 1.5 mg daily.
Can be increased to a maximum dose of 3 mg
daily.
• If EVG/c is withdrawn, cariprazine dose may
need to be increased.
Starting EVG/c in a Patient Already on
Cariprazine:
• For patients receiving cariprazine 3 mg or 6 mg
daily, reduce cariprazine dose by half.
• For patients taking cariprazine 4.5 mg daily, the
dose should be reduced to 1.5 mg or 3 mg daily.
• For patients taking cariprazine 1.5 mg daily,
change to 1.5 mg every other day.
• If EVG/c is withdrawn, cariprazine dose may
need to be increased.

INSTI
Antidepressants/Anxiolytics/Antipsychotics, continued
Also see Sedative/Hypnotics section below.
Fluvoxamine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ or ↓ EVG possible Consider alternative antidepressant or ARV.
Lurasidone BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ lurasidone expected Contraindicated.
Pimavanserin BIC, DTG, RAL ↔ expected Standard doses.
EVG/c ↑ pimavanserin expected Reduce pimavanserin dose by 50%. Titrate
dose based on efficacy and toxicity.
Pimozide BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ pimozide expected Contraindicated.
Quetiapine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ quetiapine AUC expected Initiation of Quetiapine in a Patient Receiving
EVG/c:
• Start quetiapine at the lowest dose and titrate
up as needed. Monitor for quetiapine efficacy
and adverse effects.
Initiation of EVG/c in a Patient Receiving a
Stable Dose of Quetiapine:
• Reduce quetiapine dose to 1/6 of the original
dose, and closely monitor for quetiapine
efficacy and adverse effects.
SSRIs EVG/c ↔ EVG No dose adjustment necessary.
Citalopram, ↔ sertraline
escitalopram,
fluoxetine, paroxetine, ↑ other SSRI possible Initiate with lowest dose of SSRI and titrate
sertraline dose carefully based on antidepressant
response.
BIC, DTG, RAL ↔ BIC, DTG, RAL expected No dose adjustment necessary.
↔ SSRI expected
TCAs BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Amitriptyline, EVG/c Desipramine AUC ↑ 65% Initiate with lowest dose of TCA and titrate dose
desipramine, carefully.
doxepin, imipramine, ↑ TCA expected Initiate with lowest dose of TCA and titrate dose
nortriptyline carefully based on antidepressant response
and/or drug levels.
Trazodone BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ trazodone possible Initiate with lowest dose of trazodone and titrate
dose carefully.
Other EVG/c ↑ antipsychotic possible Initiate antipsychotic at a low dose. Decrease in
Antipsychotics antipsychotic dose may be necessary.
(CYP3A4 and/or
CYP2D6 substrates)

INSTI
Antifungals
Isavuconazole BIC ↑ BIC possible No dose adjustment necessary.
EVG/c ↑ isavuconazole expected If coadministered, consider monitoring
isavuconazole concentrations and assess
↑ EVG and COBI possible virologic response.
Itraconazole BIC ↑ BIC expected No dose adjustment necessary.
DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ itraconazole expected Consider monitoring itraconazole level to guide
dosage adjustments. High itraconazole doses
↑ EVG and COBI possible (>200 mg/day) are not recommended unless
dose is guided by itraconazole levels.
Posaconazole BIC ↑ BIC expected No dose adjustment necessary.
EVG/c ↑ EVG and COBI possible If coadministered, monitor posaconazole
concentrations.
Voriconazole BIC ↑ BIC possible No dose adjustment necessary.
EVG/c ↑ voriconazole expected Do not coadminister voriconazole and
COBI unless benefit outweighs risk.
↑ EVG and COBI possible If coadministered, consider monitoring
voriconazole concentrations and adjust dose
accordingly.
Antihyperglycemics
Metformin BIC Metformin AUC ↑ 39% Monitor for metformin adverse effects.
DTG DTG 50 mg Once Daily plus Metformin 500 Start metformin at lowest dose and titrate based
mg BID: on glycemic control. Monitor for metformin
• Metformin AUC ↑ 79% and Cmax ↑ 66% adverse effects.
DTG 50 mg BID plus Metformin 500 mg BID: When starting/stopping DTG in patients on
metformin, dose adjustment of metformin may
• Metformin AUC ↑ 2.4-fold and Cmax ↑ 2-fold be necessary to maintain optimal glycemic
control and/or minimize adverse effects of
metformin.
RAL ↔ expected No dose adjustment necessary.
Saxagliptin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ saxagliptin expected Limit saxagliptin dose to 2.5 mg once daily.
Dapagliflozin/ BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Saxagliptin EVG/c ↑ saxagliptin expected Do not coadminister, as this coformulated
drug contains 5 mg of saxagliptin.
Antimycobacterials
Clarithromycin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ clarithromycin possible CrCl 50−60 mL/min:
↑ COBI possible • Reduce clarithromycin dose by 50%
CrCl <50 mL/min:
• EVG/c is not recommended.

INSTI
Antimycobacterials, continued
Rifabutin BIC Rifabutin (300 mg Once Daily): Do not coadminister.
• BIC AUC ↓ 38% and Cmin ↓ 56%
DTG Rifabutin (300 mg Once Daily): No dose adjustment necessary.
• DTG AUC ↔ and Cmin ↓ 30%
EVG/c Rifabutin 150 mg Every Other Day with EVG/c Do not coadminister.
Once Daily Compared to Rifabutin 300 mg
Once Daily Alone:
• ↔ rifabutin AUC
• 25-O-desacetyl-rifabutin AUC ↑ 625%
• EVG AUC ↓ 21% and Cmin ↓ 67%
RAL RAL AUC ↑ 19% and Cmin ↓ 20% No dose adjustment necessary.
Rifampin BIC BIC AUC ↓ 75% Contraindicated.
DTG Rifampin with DTG 50 mg BID Compared to Dose:
DTG 50 mg BID Alone: • DTG 50 mg BID (instead of 50 mg once daily)
• DTG AUC ↓ 54% and Cmin ↓ 72% for patients without suspected or documented
INSTI mutation.
Rifampin with DTG 50 mg BID Compared to
DTG 50 mg Once Daily Alone: Alternative to rifampin should be used in
• DTG AUC ↑ 33% and Cmin ↑ 22% patients with certain suspected or documented
INSTI-associated resistance substitutions.
Consider using rifabutin.
EVG/c Significant ↓ EVG and COBI expected Contraindicated.
RAL RAL 400 mg: Dose:
• RAL AUC ↓ 40% and Cmin ↓ 61% • RAL 800 mg BID, instead of 400 mg BID
Rifampin with RAL 800 mg BID Compared to Do not coadminister RAL 1200 mg once
RAL 400 mg BID Alone: daily with rifampin.
AL AUC ↑ 27% and Cmin ↓ 53%
•R Monitor closely for virologic response or
consider using rifabutin as an alternative
rifamycin.
Rifapentine BIC, DTG, Significant ↓ BIC, DTG, EVG, and COBI Do not coadminister.
EVG/c expected
RAL Rifapentine 900 mg Once Weekly: For once-weekly rifapentine, use standard RAL
• RAL AUC ↑ 71% and Cmin ↓ 12% 400 mg BID doses.
Rifapentine 600 mg Once Daily: Do not coadminister with once-daily

rifapentine.
•R
AL Cmin ↓ 41%

INSTI
Cardiac Medications
Antiarrhythmics BIC, DTG ↔ expected for the listed antiarrhythmics, No dose adjustment necessary.
except for disopyramide
Amiodarone, Coadminister with caution. Clinical monitoring is
bepridil, digoxin, ↑ disopyramide possible recommended.
disopyramide, RAL ↔ expected for the listed antiarrhythmics No dose adjustment necessary.
dronedarone,
flecainide, systemic EVG/c ↑ antiarrhythmics possible Use antiarrhythmics with caution. TDM, if
lidocaine, mexilitine, available, is recommended for antiarrhythmics.
Digoxin Cmax ↑ 41% and no significant change
propafenone, in AUC
quinidine
Bosentan BIC, DTG ↓ BIC, DTG possible Standard doses.
EVG/c ↑ bosentan possible In Patients on EVG/c ≥10 Days:
• Start bosentan at 62.5 mg once daily or every
other day based on individual tolerability.
In Patients on Bosentan Who Require EVG/c:
• Stop bosentan ≥36 hours before EVG/c
initiation. At least 10 days after initiation of
EVG/c, resume bosentan at 62.5 mg once
daily or every other day based on individual
tolerability.
Beta-blockers BIC, DTG, RAL ↔ expected No dose adjustment necessary.
(e.g., metoprolol, EVG/c ↑ beta-blockers possible Beta-blocker dose may need to be decreased;
timolol) adjust dose based on clinical response.
Consider using beta-blockers that are not
metabolized by CYP450 enzymes (e.g.,
atenolol, labetalol, nadolol, sotalol).
CCBs BIC ↑ BIC possible with diltiazem No dose adjustment necessary.
↔ expected for all other CCBs
EVG/c ↑ CCBs possible Coadminister with caution. Titrate CCB dose
and monitor for CCB efficacy and toxicities.
Refer to Table 19a for diltiazem plus ATV/r
recommendations.
Dofetilide BIC, DTG ↑ dofetilide expected Contraindicated.
EVG/c ↑ dofetilide possible Do not coadminister.
Eplerenone BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ eplerenone expected Contraindicated.
Ranolazine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ ranolazine expected Contraindicated.
Ivabradine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ ivabradine expected Contraindicated.

INSTI
Corticosteroids
Beclomethasone BIC, DTG, ↔ expected No dose adjustment necessary.
Inhaled or intranasal EVG/c, RAL
Budesonide, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Ciclesonide, EVG/c ↑ glucocorticoid possible Coadministration can result in adrenal
Fluticasone, insufficiency and Cushing’s syndrome.
Mometasone Do not coadminister unless potential
Inhaled or intranasal benefits of inhaled or intranasal
corticosteroid outweigh the risks of
systemic corticosteroid adverse effects.
Consider an alternative corticosteroid (e.g.,
beclomethasone).
Betamethasone, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Budesonide EVG/c ↑ glucocorticoids possible Coadministration can result in adrenal
Systemic insufficiency and Cushing’s syndrome. Do not
↓ EVG possible coadminister unless potential benefits of
systemic budesonide outweigh the risks of
systemic corticosteroid adverse effects.
Dexamethasone BIC ↓ BIC possible Consider an alternative corticosteroid for
Systemic long-term use or an alternative ARV. If
coadministration is necessary, monitor virologic
response to ART.
EVG/c ↓ EVG and COBI possible Consider an alternative corticosteroid for long-
term use or alternative ART. If coadministration
is necessary, monitor virologic response to ART.
Prednisone, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Prednisolone EVG/c ↑ prednisolone possible Coadministration may be considered if
Systemic the potential benefits outweigh the risks
of systemic corticosteroid adverse effects.
If coadministered, monitor for adrenal
insufficiency and Cushing’s syndrome.
Betamethasone, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Methylprednisolone, EVG/c ↑ glucocorticoids expected Do not coadminister. Coadministration may
Prednisolone, result in adrenal insufficiency and Cushing’s
Triamcinolone syndrome.
Local injections,
including intra-
articular, epidural, or
intra-orbital
Hepatitis C Direct Acting Antivirals
Daclatasvir DTG ↔ daclatasvir No dose adjustment necessary.
EVG/c ↑ daclatasvir Decrease daclastavir dose to 30 mg once daily.
BIC, RAL No data No dose adjustment necessary.
Dasabuvir plus BIC, DTG No data No dose adjustment necessary.
Ombitasvir/ EVG/c No data Do not coadminister.
Paritaprevir/RTV
RAL RAL AUC ↑ 134% No dose adjustment necessary.

INSTI
Hepatitis C Direct Acting Antivirals, continued
Elbasvir/Grazoprevir BIC ↔ BIC expected No dose adjustment necessary.
DTG ↔ elbasvir No dose adjustment necessary.
↔ grazoprevir
↔ DTG
EVG/c ↑ elbasvir and ↑ grazoprevir expected Coadministration is not recommended.
RAL ↔ elbasvir No dose adjustment necessary.
↔ grazoprevir
↔ RAL with elbasvir
RAL AUC ↑ 43% with grazoprevir
Glecaprevir/ BIC ↔ BIC expected No dose adjustment necessary.
Pibrentasvir DTG, RAL No significant effect No dose adjustment necessary.
EVG/c Glecaprevir AUC ↑ 3-fold No dose adjustment necessary.
Pibrentasvir AUC ↑ 57%
EVG AUC ↑ 47%
Ledipasvir/ EVG/c/TDF/ ↑ TDF and ↑ ledipasvir expected Do not coadminister.
Sofosbuvir FTC
EVG/c/TAF/ ↔ EVG/c/TAF/FTC expected No dose adjustment necessary.
FTC
BIC, DTG, RAL ↔ DTG or RAL No dose adjustment necessary.
Simeprevir BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ simeprevir expected Coadministration is not recommended.
Sofosbuvir All INSTIs ↔ expected No dose adjustment necessary.
Sofosbuvir/ All INSTIs ↔ expected No dose adjustment necessary.
Velpatasvir
Sofosbuvir/ EVG/c When Given with Sofosbuvir/Velpatasvir/ No dose adjustment necessary.
Velpatasvir/ Voxilaprevir (400 mg/100 mg/100 mg) plus
Voxilaprevir Voxilaprevir 100 mg:
• Sofosbuvir AUC ↑ 22%
• ↔ velpatasvir
• Voxilaprevir AUC ↑ 2-fold
BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Herbal Products
St. John’s Wort BIC, DTG ↓ BIC and DTG possible Do not coadminister.
EVG/c ↓ EVG and COBI possible Contraindicated.

INSTI
Hormonal Therapies
Hormonal BIC, DTG, RAL ↔ ethinyl estradiol, norgestimate, and DTG No dose adjustment necessary.
Contraceptives or RAL
Oral EVG/c Norgestimate AUC, Cmax, and Cmin ↑ >2-fold The effects of increases in progestin
(norgestimate) are not fully known and can
Ethinyl estradiol AUC ↓ 25% and Cmin ↓ 44% include insulin resistance, dyslipidemia, acne,
and venous thrombosis. Weigh the risks and
benefits of the drug and consider using an
alternative contraceptive method.
↑ drospirenone possible Clinical monitoring is recommended, due to the
potential for hyperkalemia.
Hormonal All INSTIs No data No drug-drug interaction studies have been
Contraceptives conducted with INSTIs and non-oral routes
Non-oral of hormone administration. It is unclear if oral
drug-drug interaction data can be extrapolated
beyond oral routes of administration.
Menopausal BIC, DTG, RAL With Estradiol or Conjugated Estrogen (Equine No dose adjustment necessary.
Hormone and Synthetic):
Replacement • ↔ estrogen expected
Therapy
↔ drospirenone, medroxyprogesterone, or
micronized progesterone expected
EVG/c ↓ estrogen expected Adjust estrogen and progestin dose as needed
based on clinical effects.
↑ drospirenone possible
↑ oral medroxyprogesterone possible
↑ oral micronized progesterone possible
Gender-Affirming BIC, DTG, RAL ↔ estrogen expected No dose adjustment necessary.
Hormone Therapy BIC, DTG, ↔ finasteride, goserelin, leuprolide acetate,
EVG/c, RAL spironolactone expected
EVG/c ↓ estradiol expected Adjust dutasteride dosage as needed based
on clinical effects and endogenous hormone
↑ dutasteride possible concentrations.
EVG/c ↑ testosterone possible Monitor masculinizing effects of testosterone
and for adverse effects and adjust testosterone
dose as necessary.
BIC, DTG, RAL ↔ testosterone expected No dose adjustment necessary.
Atorvastatin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c Atorvastatin AUC ↑ 2.6-fold and Cmax ↑ 2.3-fold Titrate statin dose carefully and use the lowest
dose necessary while monitoring for toxicities.
Do not exceed 20 mg atorvastatin daily.
Lovastatin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c Significant ↑ lovastatin expected Contraindicated.
Pitavastatin, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Pravastatin EVG/c No data No dose recommendation.

INSTI
HMG-CoA Reductase Inhibitors, continued
Rosuvastatin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c Rosuvastatin AUC ↑ 38% and Cmax ↑ 89% Titrate statin dose carefully and use the lowest
dose necessary while monitoring for toxicities.
Simvastatin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c Significant ↑ simvastatin expected Contraindicated.
Immunosuppressants
Cyclosporine, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Everolimus, EVG/c ↑ immunosuppressant possible Initiate with an adjusted immunosuppressant
Sirolimus, dose to account for potential increased
Tacrolimus concentration and monitor for toxicities.
Therapeutic drug monitoring of
immunosuppressant is recommended. Consult
with a specialist as necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine BIC, DTG ↔ expected No dose adjustment necessary.
Sublingual, buccal, or EVG/c Buprenorphine AUC ↑ 35% and Cmin ↑ 66% No dose adjustment necessary. Clinical
implant monitoring is recommended. When
Norbuprenorphine AUC ↑ 42% and Cmin ↑ 57% transferring buprenorphine from transmucosal
administration to implantation, monitor to
ensure buprenorphine effect is adequate and
not excessive.
RAL ↔ observed (sublingual) No dose adjustment necessary.
↔ expected (implant)
Methadone All INSTIs No significant effect No dose adjustment necessary.
PDE5 Inhibitors
Avanafil BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c No data Coadministration is not recommended.
Sildenafil BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ sildenafil expected For Treatment of Erectile Dysfunction:
• Start with sildenafil 25 mg every 48 hours and
monitor for adverse effects of sildenafil.
For treatment of PAH:
• Contraindicated.

INSTI
PDE5 Inhibitors, continued
Tadalafil BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ tadalafil expected For Treatment of Erectile Dysfunction:
• Start with tadalafil 5-mg dose and do not
exceed a single dose of tadalafil 10 mg every
72 hours. Monitor for adverse effects of
tadalafil.
For Treatment of PAH
In Patients on EVG/c >7 Days:
• Start with tadalafil 20 mg once daily and
increase to tadalafil 40 mg once daily based
on tolerability.
In Patients on Tadalafil who Require EVG/c:
• Stop tadalafil ≥24 hours before EVG/c
initiation. Seven days after EVG/c initiation,
restart tadalafil at 20 mg once daily, and
increase to tadalafil 40 mg once daily based
on tolerability.
Vardenafil BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ vardenafil expected Start with vardenafil 2.5 mg every 72 hours and
monitor for adverse effects of vardenafil.
Sedative/Hypnotics
Clonazepam, BIC, DTG, RAL ↔ expected No dose adjustment necessary.
Clorazepate, EVG/c ↑ benzodiazepines possible Dose reduction of benzodiazepine may be
Diazepam, necessary. Initiate with low dose and clinically
Estazolam, monitor.
Flurazepam
Consider alternative benzodiazepines to
diazepam, such as lorazepam, oxazepam, or
temazepam.
Midazolam, BIC, RAL ↔ expected No dose adjustment necessary.
Triazolam DTG With DTG 25 mg: No dose adjustment necessary.
• ↔ Midazolam AUC
EVG/c ↑ midazolam expected Contraindicated. Do not coadminister
triazolam or oral midazolam and EVG/c.
↑ triazolam expected
Parenteral midazolam can be used with caution
in a closely monitored setting. Consider dose
reduction, especially if >1 dose is administered.
Suvorexant BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ suvorexant expected Coadministration is not recommended.
Zolpidem BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ zolpidem expected Initiate zolpidem at a low dose. Dose reduction
may be necessary.

INSTI
Miscellaneous Drugs
Calcifediol BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ calcifediol possible Dose adjustment of calcifediol may be required,
and serum 25-hydroxyvitamin D, intact PTH,
and serum Ca concentrations should be closely
monitored.
Cisapride BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ cisapride expected Contraindicated.
Colchicine BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ colchicine expected Do not coadminister in patients with hepatic
or renal impairment.
For Treatment of Gout Flares:
• Administer colchicine 0.6 mg for 1 dose,
followed by colchicine 0.3 mg 1 hour later. Do
not repeat dose for at least 3 days.
For Prophylaxis of Gout Flares:
• If original dose was colchicine 0.6 mg BID,
decrease to colchicine 0.3 mg once daily. If
regimen was 0.6 mg once daily, decrease to
0.3 mg every other day.
For Treatment of Familial Mediterranean Fever:
• Do not exceed colchicine 0.6 mg once daily or
0.3 mg BID.
Enzalutamide DTG ↓ DTG possible Monitor for ARV efficacy.
BIC, EVG/c ↓ BIC, EVG/c expected Contraindicated.
Ergot Derivatives BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ dihydroergotamine, ergotamine, Contraindicated.
methylergonovine expected
Dronabinol BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ dronabinol possible Monitor for dronabinol-related adverse effects.
Eluxadoline BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ eluxadoline possible Monitor for eluxadoline-related adverse effects.
Flibanserin BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ flibanserin expected Contraindicated.
Mitotane BIC, EVG/c ↓ BIC and ↓ EVG/c expected Contraindicated.
DTG ↓ DTG possible Monitor for ARV efficacy.

INSTI
Miscellaneous Drugs, continued
Polyvalent Cation BIC ↔ BIC AUC if given simultaneously with Fe or With Supplements that Contain Ca or Fe:
Supplements Ca and food • BIC and supplements containing Ca or Fe can
Mg, Al, Fe, Ca, be taken together with food.
Zn, including BIC AUC ↓ 33% if given simultaneously with
multivitamins with CaCO3 under fasting conditions Do not coadminister BIC under fasting
minerals BIC AUC ↓ 63% if given simultaneously with conditions simultaneously with, or 2 hours
Fe under fasting conditions after, supplements containing Ca or Fe.
Note: Please refer
to the Acid Reducers DTG DTG AUC ↓ 39% if given simultaneously with With Supplements That Contain Ca or Fe:
section in this table calcium carbonate under fasting conditions • DTG and supplements containing Ca or Fe
for recommendations can be taken together with food; alternately,
on use with Al-, Mg-, DTG AUC ↓ 54% if given simultaneously with
Fe under fasting conditions administer DTG at least 2 hours before or at
and Ca-containing least 6 hours after supplement.
antacids. ↔ DTG when administered with Ca or Fe
supplement simultaneously with food Do not coadminister DTG under fasting
conditions simultaneously with, or 2 hours
after, supplements containing Ca or Fe.
EVG/c, RAL ↓ INSTI possible If coadministration is necessary, give INSTI at
least 2 hours before or at least 6 hours after
supplements containing polyvalent cations,
including but not limited to the following
products: cation-containing laxatives; Fe, Ca,
or Mg supplements; and sucralfate. Monitor for
virologic efficacy.
Many oral multivitamins also contain varying
amounts of polyvalent cations; the extent and
significance of chelation is unknown.
Salmeterol BIC, DTG, RAL ↔ expected No dose adjustment necessary.
EVG/c ↑ salmeterol possible Do not coadminister, due to potential
increased risk of salmeterol-associated
cardiovascular events.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: Al = aluminum; ART = antiretroviral therapy; ARV = antiretroviral; ATV/r = atazanavir/ritonavir; AUC = area under the
curve; BIC = bictegravir; BID = twice daily; Ca = calcium; CaCO3 = calcium carbonate; CCB = calcium channel blocker; Cmax = maximum
plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; CrCl = creatinine clearance; CYP = cytochrome P;
DTG = dolutegravir; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; Fe = iron; FTC = emtricitabine; INR= international normalized
ratio; INSTI = integrase strand transfer inhibitor; Mg = magnesium; PAH = pulmonary arterial hypertension; PI = protease inhibitor; PK =
pharmacokinetic; PTH = parathyroid hormone; RAL = raltegravir; RTV = ritonavir; SSRI = selective serotonin reuptake inhibitors; TAF =
tenofovir alafenamide; TCA = tricyclic antidepressants; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; Zn = zinc

Table 19e. Drug Interactions between CCR5 Antagonist (Maraviroc) and Other Drugs (Including
Antiretroviral Agents) (Last updated October 25, 2018; last reviewed October 25, 2018) (page 1 of 3)
In the table below, “No dose adjustment necessary” indicates that the FDA-approved dose of MVC 300
mg twice daily should be used. Recommendations for managing a particular drug interaction may differ
depending on whether a new ARV is being initiated in a patient on a stable concomitant medication
or whether a new concomitant medication is being initiated in a patient on a stable ARV regimen. The
magnitude and significance of drug interactions are difficult to predict when several drugs with competing
metabolic pathways are prescribed concomitantly.
Effect on CCR5 Antagonist

Concomitant Drug Class/ CCR5 Dosing Recommendations and Clinical
and/or Concomitant Drug
Name Antagonist Comments
Concentrations
Anticonvulsants
Carbamazepine, MVC ↓ MVC possible If used without a strong CYP3A inhibitor, use MVC 600
Phenobarbital, Phenytoin mg BID or an alternative antiepileptic agent.
Antifungals
Isavuconazole MVC ↑ MVC possible Consider dose reduction to MVC 150 mg BID.
Itraconazole MVC ↑ MVC possible Dose:
• MVC 150 mg BID
Posaconazole MVC ↑ MVC possible Dose:
• MVC 150 mg BID
Voriconazole MVC ↑ MVC possible Consider dose reduction to MVC 150 mg BID.
Antimycobacterials
Clarithromycin MVC ↑ MVC possible Dose:
• MVC 150 mg BID
Rifabutin MVC ↓ MVC possible If used without a strong CYP3A inducer or inhibitor, no
dose adjustment is necessary.
If used with a strong CYP3A inhibitor, use MVC 150 mg
BID.
Rifampin MVC MVC AUC ↓ 64% Dose:
• MVC 600 mg BID
If used with a strong CYP3A inhibitor, use MVC 300 mg
BID.
Rifapentine MVC ↓ MVC expected Do not coadminister.
Hepatitis C Direct-Acting Antivirals
Daclatasvir MVC ↔ MVC expected No dose adjustment necessary.
↔ daclatasvir expected
Dasabuvir plus MVC ↑ MVC expected Do not coadminister.
Ombitasvir/Paritaprevir/
RTV
Elbasvir/Grazoprevir MVC ↔ MVC expected No dose adjustment necessary.
Ledipasvir/Sofosbuvir MVC ↔ MVC expected No dose adjustment necessary.
Glecaprevir/Pibrentasvir MVC ↔ MVC expected No dose adjustment necessary.
Simeprevir MVC ↔ MVC expected No dose adjustment necessary.
Sofosbuvir MVC ↔ MVC expected No dose adjustment necessary.
Sofosbuvir/Velpatasvir MVC ↔ MVC expected No dose adjustment necessary.

Concentrations
Hepatitis C Direct-Acting Antivirals, continued
Sofosbuvir/Velpatasvir/ MVC ↔ MVC expected No dose adjustment necessary.
Voxilaprevir
Herbal Products
St. John’s Wort MVC ↓ MVC expected Do not coadminister.
Hormonal Therapies
Hormonal Contraceptives MVC ↔ Ethinyl estradiol or No dose adjustment necessary.
levonorgestrel
Menopausal Hormone MVC ↔ MVC or hormone No dose adjustment necessary.
Replacement Therapy replacement therapies expected
Gender-Affirming MVC ↔ MVC or gender-affirming No dose adjustment necessary.
Hormone Therapies hormones expected
ARV Drugs
INSTIs
BIC, DTG MVC ↔ MVC expected No dose adjustment necessary.
EVG/c MVC ↑ MVC possible Dose:
• MVC 150 mg BID
RAL MVC MVC AUC ↓ 21% No dose adjustment necessary.
RAL AUC ↓ 37%
NNRTIs
DOR, RPV MVC ↔ MVC expected No dose adjustment necessary.
EFV MVC MVC AUC ↓ 45% Dose:
• MVC 600 mg BID
ETR MVC MVC AUC ↓ 53% Dose:
• MVC 600 mg BID in the absence of a potent CYP3A
inhibitor
NVP MVC ↔ MVC AUC Without HIV PI:
• MVC 300 mg BID
With HIV PI (Except TPV/r):
• MVC 150 mg BID
PIs
ATV with or without RTV MVC With Unboosted ATV: Dose:
or COBI • MVC AUC ↑ 257% • MVC 150 mg BID
With (ATV/r 300 mg/100 mg)
Once Daily:
• MVC AUC ↑ 388%

Concentrations
PIs, continued
DRV/c MVC With (DRV/r 600 mg/100 mg) Dose:
or BID: • MVC 150 mg BID
DRV/r • MVC AUC ↑ 305%
With (DRV/r 600 mg/100 mg)
BID and ETR:
• MVC AUC ↑ 210%
LPV/r MVC MVC AUC ↑ 295% Dose:
With LPV/r and EFV: • MVC 150 mg BID
• MVC AUC ↑ 153%
RTV MVC With RTV 100 mg BID: Dose:
• MVC AUC ↑ 161% • MVC 150 mg BID
TPV/r MVC With (TPV/r 500 mg/200 mg) No dose adjustment necessary.
BID:
• ↔ MVC AUC
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: ARV = antiretroviral; ATV = atazanavir; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir;
BID = twice daily; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r
= darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FDA = Food and Drug
Administration; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse
transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir;
TPV/r = tipranavir/ritonavir

Table 20a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease
Inhibitors (Last updated October 25, 2018; last reviewed October 25, 2018) (page 1 of 2)
Note: Delavirdine (DLV), fosamprenavir (FPV), indinavir (IDV), nelfinavir (NFV), and saquinavir (SQV) are not included
in this table. Please refer to the Food and Drug Administration product labels for DLV, FPV, IDV, NFV, and SQV for
information regarding drug interactions.
NNRTIs
PIs
DOR EFV ETR NVP RPVa
ATV PK ↑ DOR expected ↔ EFV ETR AUC ↑ 50% and ↓ ATV possible ↑ RPV possible
Data Cmin ↑ 58%
Unboosted ↔ ATV expected ATV AUC ↓ 74%
ATV AUC ↓ 17% and
Cmin ↓ 47%
Dose Standard doses Do not coadminister. Do not coadminister. Do not coadminister. Standard doses
ATV/c PK ↑ DOR expected ↓ ATV possible ↓ ATV possible ↓ ATV possible ↑ RPV possible
Data
↔ ATV expected ↓ COBI possible ↓ COBI possible ↓ COBI possible ↔ ATV expected
Dose Standard doses EFV standard dose Do not coadminister. Do not coadminister. Standard doses
In ART-Naive Patients:
• ATV 400 mg plus COBI 150
mg once daily
• Do not use coformulated
ATV/c 300 mg/150 mg.
In ART-Experienced Patients:
• Do not coadminister.
ATV/r PK ↑ DOR expected (ATV 400 mg plus RTV 100 (ATV 300 mg plus RTV (ATV 300 mg plus ↑ RPV possible
Data mg) Once Daily: 100 mg) Once Daily: RTV 100 mg) Once
↔ ATV expected Daily:
• ATV concentrations similar • ETR AUC and Cmin
to (ATV 300 mg plus RTV both ↑ ~30% • ATV AUC ↓ 42% and
100 mg) without EFV • ↔ ATV AUC and Cmin Cmin ↓ 72%
• NVP AUC ↑ 25%
Dose Standard doses EFV standard dose ETR standard dose Do not coadminister. Standard doses
In ART-Naive Patients: (ATV 300 mg plus RTV
• (ATV 400 mg plus RTV 100 100 mg) once daily
mg) once daily
In ART-Experienced Patients:
• Do not coadminister.
DRV/c PK ↑ DOR expected ↓ DRV possible ETR 400 mg Once ↓ DRV possible ↔ DRV expected
Data Daily with (DRV 800
↔ DRV ↓ COBI possible mg plus COBI 150 mg) ↓ COBI possible ↑ RPV possible
expected Once Daily:
• ↔ ETR AUC and Cmin
• ↔ DRV AUC and Cmin
↓ 56%
• COBI AUC ↓ 30% and
Cmin ↓ 66%
Dose Standard doses Do not coadminister. Do not coadminister. Do not coadminister. Standard doses

Table 20a. Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors and Protease
Inhibitors (Last updated October 25, 2018; last reviewed October 25, 2018) (page 2 of 2)
NNRTIs
PIs
DOR EFV ETR NVP RPVa
DRV/r PK ↑ DOR expected With (DRV 300 mg plus RTV ETR 100 mg BID with With (DRV 400 mg RPV 150 mg Once
Data 100 mg) BID: (DRV 600 mg plus RTV plus RTV 100 mg) Daily with (DRV
↔ DRV 100 mg) BID: BID: 800 mg plus RTV
expected • EFV AUC ↑ 21%
• ETR AUC ↓ 37% and • NVP AUC ↑ 27% 100 mg) Once
• ↔ DRV AUC and Cmin ↓ Daily:
31% Cmin ↓ 49% and Cmin ↑ 47%
• ↔ DRV • DRV AUC ↑ 24%b • RPV AUC ↑ 130%
and Cmin ↑ 178%
• ↔ DRV
Dose Standard doses Clinical significance unknown. Standard doses Standard doses Standard doses
Use standard doses and
monitor patient closely. Despite reduced ETR
Consider monitoring drug concentration, safety
levels. and efficacy of this
combination have been
established in a clinical
trial.
LPV/r PK ↑ DOR expected With LPV/r Tablets 500 With LPV/r Tablets: With LPV/r Capsules: RPV 150 mg Once
Data mg/125 mgc BID: • ETR AUC ↓ 35% • LPV AUC ↓ 27% and Daily with LPV/r
↔ LPV Capsules:
expected • LPV concentration similar (comparable to the C ↓ 51%
min
to that of LPV/r 400 mg/100 decrease with DRV/r) • RPV AUC ↑ 52%
mg BID without EFV • ↔ LPV AUC and Cmin ↑ 74%
• ↔ LPV
Dose Standard doses LPV/r tablets 500 mg/125 mgc Standard doses LPV/r tablets 500 Standard doses
BID; LPV/r oral solution 533 mg/125 mgc BID;
mg/133 mg BID LPV/r oral solution
533 mg/133 mg BID
EFV standard dose
NVP standard dose
TPV/r PK ↑ DOR expected With (TPV 500 mg plus RTV With (TPV 500 mg plus With (TPV 250 mg ↑ RPV possible
Data 100 mg) BID: RTV 200 mg) BID: plus RTV 200 mg)
Always ↔ TPV BID or with (TPV 750
use TPV expected • ↔ EFV • ETR AUC ↓ 76% and
Cmin ↓ 82% mg plus RTV 100 mg)
with RTV • TPV AUC ↓ 31% and Cmin BID:
↓ 42% • ↔ TPV AUC and Cmin
↑ 24% • ↔ NVP
With (TPV 750 mg plus RTV • ↔ TPV expected
200 mg) BID:
• ↔ EFV and TPV
Dose Standard doses Standard doses Do not coadminister. Standard doses Standard doses
a
Approved dose for RPV is 25 mg once daily. Most PK studies were performed using RPV 75 mg to 150 mg per dose.
b
DRV concentration was compared to a historic control.
c
Use a combination of two LPV/r 200 mg/50 mg tablets plus one LPV/r 100 mg/25 mg tablet to make a total dose of LPV/r 500 mg/125 mg.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: ART = antiretroviral therapy; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under
the curve; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/
cobicistat; DRV/r = darunavir/ritonavir; EFV = efavirenz; ETR = etravirine; LPV = lopinavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside
reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir

Table 20b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse
Transcriptase Inhibitors or Protease Inhibitors (Last updated October 25, 2018; last reviewed
October 25, 2018) (page 1 of 3)
is being initiated in a patient on a stable concomitant medication or if a new concomitant medication is being
initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are
ARV Drugs by INSTIs
Drug Class BIC DTG EVG/c RAL
NNRTIs
DOR PK ↔ DOR, BIC ↔ DOR ↑ DOR expected ↔ DOR, RAL expected
Data expected
DTG AUC ↑ 36% and Cmin ↑ 27% ↔ EVG
Dose Standard doses Standard doses Standard doses Standard doses
EFV PK ↓ BIC expected With DTG 50 mg Once Daily: ↑ or ↓ EVG, COBI, With RAL 400 mg BID:
Data • DTG AUC ↓ 57% and Cmin ↓ 75% EFV possible • RAL AUC ↓ 36% and
Cmin ↓ 21%
With RAL 1200 mg Once
Daily:
• RAL AUC ↓ 14% and
↔ Cmin
Dose Do not In Patients Without INSTI Resistance: Do not coadminister. Standard doses
coadminister. • DTG 50 mg BID
In Patients With Certain INSTI-
Associated Resistancea or Clinically
Suspected INSTI Resistance:
• Consider alternative combination.
ETR PK ↓ BIC expected ETR 200 mg BID plus DTG 50 mg ↑ or ↓ EVG, COBI, ETR 200 mg BID plus
Data Once Daily: ETR possible RAL 400 mg BID:
• DTG AUC ↓ 71% and Cmin ↓ 88% • ETR Cmin ↑ 17%
ETR 200 mg BID with (DRV 600 mg • RAL Cmin ↓ 34%
plus RTV 100 mg) BID and DTG 50
mg Once Daily:
• DTG AUC ↓ 25% and Cmin ↓ 37%
ETR 200 mg BID with (LPV 400 mg
plus RTV 100 mg) BID and DTG 50
mg Once Daily:
• DTG AUC ↑ 11% and Cmin ↑ 28%

ARV Drugs by INSTIs
NNRTIs, continued
ETR, Dose Do not Do not coadminister ETR and DTG Do not coadminister. RAL 400 mg BID
continued coadminister. without concurrently administering
ATV/r, DRV/r, or LPV/r. Coadministration with
RAL 1200 mg once daily
In Patients Without INSTI Resistance: is not recommended.
• DTG 50 mg once daily with ETR
(concurrently with ATV/r, DRV/r, or
LPV/r)
In Patients With Certain INSTI-
Associated Resistancea or Clinically
• DTG 50 mg BID with ETR
(concurrently with ATV/r, DRV/r, or
LPV/r)
NVP PK ↓ BIC expected With DTG 50 mg Once Daily: ↑ or ↓ EVG, COBI, No data
Data • DTG AUC ↓ 19% and Cmin ↓ 34% NVP possible
Dose Do not Standard doses Do not coadminister. Standard doses
coadminister.
RPV PK No data With DTG 50 mg Once Daily: ↑ or ↓ EVG, COBI, ↔ RPV
Data • DTG AUC ↔ and Cmin ↑ 22% RPV possible
RAL Cmin ↑ 27%
• RPV AUC ↔ and Cmin ↑ 21%
Dose Standard doses Standard doses Do not coadminister. Standard doses
PIs
ATV/c PK BIC AUC ↑ 305% No data No data No data
Data
coadminister.
ATV PK BIC AUC ↑ 310% Unboosted ATV plus DTG 30 mg ↑ or ↓ EVG, COBI, With Unboosted ATV:
+/- Data Once Daily: ATV possible • RAL AUC ↑ 72%
RTV • DTG AUC ↑ 91% and Cmin ↑ 180%
With Unboosted ATV and
(ATV 300 mg plus RTV 100 mg) RAL 1200 mg:
Once Daily plus DTG 30 mg Once • RAL AUC ↑ 67%
Daily:
• DTG AUC ↑ 62% and Cmin ↑ 121% With (ATV 300 mg plus
RTV 100 mg) Once Daily:
• RAL AUC ↑ 41%
coadminister.
DRV/c PK BIC AUC ↑ 74% DRV/c plus DTG Once Daily: DRV/c plus EVG/c: No data
Data • ↔ DTG, DRV, COBI • ↓ EVG possible
DTG 50 mg Once Daily and DRV/r
Once Daily Switched to DRV/c:
• DTG Cmin ↑ 100%

ARV Drugs by INSTIs
PIs, continued
DRV/r PK No data (DRV 600 mg plus RTV 100 mg) BID ↑ or ↓ EVG, COBI, With (DRV 600 mg plus
Data with DTG 30 mg Once Daily: DRV possible RTV 100 mg) BID:
• DTG AUC ↓ 22% and Cmin ↓ 38% • RAL AUC ↓ 29% and
Cmin ↑ 38%
LPV/r PK No data With (LPV 400 mg plus RTV 100 mg) ↑ or ↓ EVG, COBI, ↓ RAL
Data BID and DTG 30 mg Once Daily: LPV possible
↔ LPV/r
• ↔ DTG RTV and COBI have
similar effects on
CYP3A.
Dose Consider alternative Standard doses Do not coadminister. Standard doses
combination.
TPV/r PK ↓ BIC possible With (TPV 500 mg plus RTV 200 mg) ↑ or ↓ EVG, COBI, With (TPV 500 mg plus
Data BID and DTG 50 mg Once Daily: TPV possible RTV 200 mg) BID and
• DTG AUC ↓ 59% and Cmin ↓ 76% RAL 400 mg BID:
RTV and COBI have
similar effects on • RAL AUC ↓ 24% and
CYP3A. Cmin ↓ 55%
Dose Do not In Patients Without INSTI Resistance: Do not coadminister. RAL 400 mg BID
coadminister. • DTG 50 mg BID Coadministration with
In Patients With Certain INSTI- RAL 1200 mg once daily
Associated Resistancea or Clinically is not recommended.
• Consider alternative combination.
a
Refer to DTG product labeling for details.
Key to Symbols:
↑ = increase
↓ = decrease
↔ = no change
Key to Acronyms: ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under
the curve; BIC = bictegravir; BID = twice daily; Cmin = minimum plasma concentration; COBI = cobicistat; CYP = cytochrome P; DOR
= doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR =
etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = lopinavir/
ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL =
raltegravir; RPV = rilpivirine; RTV = ritonavir; TPV = tipranavir; TPV/r = tipranavir/ritonavir

Appendix B, Table 1. Characteristics of Nucleoside Reverse Transcriptase Inhibitors (Last updated
October 25, 2018; last reviewed October 25, 2018) (page 1 of 6)
Generic Name Serum/
Dosing Elimination/
(Abbreviation) Formulations Intracellular Adverse Eventsb
Recommendationsa Metabolic Pathway
Trade Name Half-Lives
Abacavir Ziagen: Ziagen: Metabolized by alcohol 1.5 hours/ • HSRs: Patients who test
(ABC) • 300 mg tablet • 600 mg once daily, or dehydrogenase and 12–26 hours positive for HLA-B*5701 are
Ziagen glucuronyl transferase at highest risk. HLA screening
• 20 mg/mL oral • 300 mg BID should be done before
Note: Generic solution Renal excretion of initiation of ABC.
tablet formulation Take without regard to metabolites: 82%
is available. meals. • For patients with a history
Dose adjustment for of HSR, re challenge is not
(ABC/3TC) Epzicom: Epzicom: ABC is recommended recommended.
Epzicom • (ABC 600 mg plus • 1 tablet once daily in patients with hepatic • Symptoms of HSR may
Note: Generic 3TC 300 mg) tablet insufficiency (see include fever, rash, nausea,
formulation is Appendix B, Table 8). vomiting, diarrhea, abdominal
available. pain, malaise, fatigue, or
(ABC/DTG/3TC) Triumeq: Triumeq: respiratory symptoms such
Triumeq as sore throat, cough, or
• (ABC 600 mg plus • 1 tablet once daily shortness of breath.
3TC 300 mg plus
DTG 50 mg) tablet • Some cohort studies suggest
increased risk of MI with
(ABC/ZDV/3TC) Trizivir: Trizivir: recent or current use of
Trizivir • (ABC 300 mg plus • 1 tablet BID ABC, but this risk is not
Note: Generic ZDV 300 mg plus substantiated in other studies.
formulation is 3TC 150 mg) tablet
available.
Didanosine Videx EC: Body Weight ≥60 kg: Renal excretion: 50% 1.5 hours/ • Pancreatitis
(ddI) • 125, 200, 250, and • ddI 400 mg once daily >20 hours • Peripheral neuropathy
Videx Dose adjustment
400 mg capsules is recommended in • Retinal changes, optic neuritis
Videx EC With TDF:
Videx: patients with renal • Lactic acidosis with hepatic
Note: Generic • ddI 250 mg once daily insufficiency (see
• 10 mg/mL oral steatosis with or without
is available as Body Weight <60 kg: Appendix B, Table 8). pancreatitis (rare but
delayed-release solution
• ddI 250 mg once daily potentially life-threatening
capsules; dose toxicity)
is the same as With TDF:
Videx EC. • Nausea, vomiting
• ddI 200 mg once daily • Potential association
Take 1/2 hour before or 2 with noncirrhotic portal
hours after a meal. hypertension; in some cases,
patients presented with
Note: Preferred dosing with esophageal varices
oral solution is BID (with the
• One cohort study suggested
total daily dose divided into
increased risk of MI with
2 doses).
recent or current use of
ddI, but this risk is not
substantiated in other studies.
• Insulin resistance/diabetes
mellitus

Generic Name Serum/
Dosing Elimination/
Emtricitabine Emtriva: Emtriva Renal excretion: 86% 10 hours/ • Minimal toxicity
(FTC) • 200 mg hard Capsule: >20 hours •H yperpigmentation/skin
Emtriva Dose adjustment
gelatin capsule • FTC 200 mg once daily is recommended in discoloration
• 10 mg/mL oral patients with renal • Severe acute exacerbation
solution Oral Solution: insufficiency (see of hepatitis may occur in
• FTC 240 mg (24 mL) once Appendix B, Table 8). HBV coinfected patients who
daily discontinue FTC.
Take without regard to
meals.
(FTC/TAF) Descovy: Descovy:
Descovy • (FTC 200 mg plus • 1 tablet once daily
TAF 25 mg) tablet
(FTC/TDF) Truvada: Truvada:
Truvada • (FTC 200 mg plus • 1 tablet once daily
TDF 300 mg) tablet
(FTC/BIC/TAF) Biktarvy: Biktarvy:
Biktarvy • (FTC 200 mg plus • 1 tablet once daily
BIC 50 mg plus
TAF 25 mg) tablet
(FTC/DRV/c/TAF) Symtuza: Symtuza:
Symtuza • (FTC 200 mg plus • 1 tablet once daily with
DRV 800 mg plus food
COBI 150 mg plus
TAF 10 mg) tablet
(FTC/EFV/TDF) Atripla: Atripla:
Atripla • (FTC 200 mg plus • 1 tablet once daily on an
EFV 600 mg plus empty stomach, preferably
TDF 300 mg) tablet at bedtime
(FTC/EVG/c/ Genvoya: Genvoya:
TAF) • (FTC 200 mg plus • 1 tablet once daily with
Genvoya EVG 150 mg plus food
COBI 150 mg plus
TAF 10 mg) tablet
(FTC/EVG/c/ Stribild: Stribild:
TDF) • (FTC 200 mg plus • 1 tablet once daily with
Stribild EVG 150 mg plus food
COBI 150 mg plus
TDF 300 mg) tablet
(FTC/RPV/TDF) Complera: Complera:
Complera • (FTC 200 mg plus • 1 tablet once daily with a
RPV 25 mg plus meal
TDF 300 mg) tablet

Generic Name Serum/
Dosing Elimination/
Lamivudine Epivir: Epivir: Renal excretion: 70% 5–7 hours/ • Minimal toxicity
(3TC) • 150 and 300 mg • 3TC 300 mg once daily, or Dose adjustment in 18–22 hours • S evere acute exacerbation
Epivir tablets of hepatitis may occur in
• 3TC 150 mg BID patients with renal
Note: Generic is • 10 mg/mL oral insufficiency is HBV coinfected patients who
available. solution recommended (see discontinue 3TC.
(3TC/ABC) Epzicom: Epzicom: Appendix B, Table 8).
Epzicom • (3TC 300 mg plus • 1 tablet once daily
Note: Generic is ABC 600 mg)
available. tablet
(3TC/TDF) Cimduo: Cimduo:
Cimduo • (3TC 300 mg plus • 1 tablet once daily
TDF 300 mg) tablet
(3TC/ZDV) Combivir: Combivir:
Combivir • (3TC 150 mg plus • 1 tablet BID
Note: Generic is ZDV 300 mg) tablet
available.
(3TC/ABC/ZDV) Trizivir: Trizivir:
Trizivir • (3TC 150 mg plus • 1 tablet BID
Note: Generic is ZDV 300 mg plus
available. ABC 300 mg)
tablet
(3TC/DOR/TDF) Delstrigo: Delstrigo:
Delstrigo • (3TC 300 mg plus • 1 tablet once daily
DOR 100 mg plus
TDF 300 mg) tablet
(3TC/DTG/ABC) Triumeq: Triumeq:
Triumeq • (3TC 300 mg plus • 1 tablet once daily
ABC 600 mg plus
DTG 50 mg) tablet
(3TC/EFV/TDF) Symfi: Symfi:
Symfi • (3TC 300 mg plus • 1 tablet once daily on an
(3TC/EFV/TDF) Symfi Lo: Symfi Lo:
Symfi Lo • (3TC 300 mg plus • 1 tablet once daily on an

Generic Name Serum/
Dosing Elimination/
Stavudine Zerit: Body Weight ≥60 kg: Renal excretion: 50% 1 hour/ • Peripheral neuropathy
(d4T) • 15, 20, 30, and 40 • d4T 40 mg BID 7.5 hours • L ipoatrophy
Zerit Dose adjustment
mg capsules is recommended in • Pancreatitis
Body Weight <60 kg:
Note: Generic is • 1 mg/mL oral patients with renal • Lactic acidosis/severe
available. solution • d4T 30 mg BID insufficiency (see hepatomegaly with hepatic
Take without regard to Appendix B, Table 8). steatosis (rare but potentially
meals. life-threatening toxicity)
Note: WHO recommends • Hyperlipidemia
30 mg BID dosing • Insulin resistance/diabetes
regardless of body weight. mellitus
• Rapidly progressive
ascending neuromuscular
weakness (rare)
Tenofovir See FDCs for HIV See FDCs for HIV Metabolized by 0.5 hours/ • Renal insufficiency, Fanconi
Alafenamide treatment below. treatment below. cathepsin A. 150–180 syndrome, proximal renal
(TAF) hours tubulopathy are less likely to
Vemlidy Not recommended in occur with TAF than with TDF.
patients with CrCl <30
Note: Available mL/min. • Osteomalacia, decrease in
as a 25-mg tablet bone mineral density are less
for the treatment likely to occur with TAF than
of HBV. with TDF.
(FTC/TAF) Descovy: Descovy: • Severe acute exacerbation
Descovy of hepatitis may occur in
• (FTC 200 mg plus • 1 tablet once daily HBV coinfected patients who
TAF 25 mg) tablet discontinue TAF.
(TAF/BIC/FTC) Biktarvy: Biktarvy: • Diarrhea, nausea, headache
Biktarvy • (TAF 25 mg plus • 1 tablet once daily
BIC 50 mg plus
FTC 200 mg) tablet
(TAF/DRV/c/FTC) Symtuza: Symtuza:
Symtuza • (TAF 10 mg plus • 1 tablet once daily with
DRV 800 mg plus food
COBI 150 mg plus
FTC 200 mg) tablet
(TAF/EVG/c/ Genvoya: Genvoya:
FTC) • (TAF 10 mg plus • 1 tablet once daily with
Genvoya EVG 150 mg plus food
COBI 150 mg plus
FTC 200 mg) tablet
(TAF/RPV/FTC) Odefsey: Odefsey:
Odefsey • (TAF 25 mg plus • 1 tablet once daily with a
RPV 25 mg plus meal
FTC 200 mg) tablet

Generic Name Serum/
Dosing Elimination/
Tenofovir Viread: Viread: Renal excretion is 17 hours/ • Renal insufficiency, Fanconi
Disoproxil • 150, 200, 250, and • TDF 300 mg once daily, or primary route of >60 hours syndrome, proximal renal
Fumarate 300 mg tablets elimination. tubulopathy
• 7.5 level scoops of oral
(TDF) • Osteomalacia, decrease in
• 40 mg/g oral powder once daily (dosing Dose adjustment
Viread bone mineral density
powder scoop dispensed with each is recommended in
Note: Generic is prescription; 1 level scoop patients with renal • Severe acute exacerbation
available. Generic: contains 1g of oral powder). insufficiency (see of hepatitis may occur in
• 300 mg tablet • Take without regard to Appendix B, Table 8 ). HBV-coinfected patients who
meals. discontinue TDF.
Mix oral powder with 2–4 • Asthenia, headache, diarrhea,
ounces of a soft food that nausea, vomiting, and
does not require chewing flatulence
(e.g., applesauce, yogurt).
Do not mix oral powder
with liquid.
(TDF/3TC) Cimduo: Cimduo:
Cimduo • (TDF 300 mg plus • 1 tablet once daily
3TC 300 mg) tablet
(TDF/FTC) Truvada: Truvada:
Truvada • (TDF 300 mg plus • 1 tablet once daily
FTC 200 mg) tablet • T
ake without regard to
meals.
(TDF/DOR/3TC) Delstrigo: Delstrigo:
Delstrigo • (TDF 300 mg plus • 1 tablet once daily
DOR 100 mg plus
3TC 300 mg) tablet
(TDF/EFV/FTC) Atripla: Atripla:
Atripla • (TDF 300 mg plus • 1 tablet once daily on an
FTC 200 mg) tablet at bedtime
(TDF/EFV/3TC) Symfi: Symfi:
Symfi • (TDF 300 mg plus • 1 tablet once daily on an
3TC 300 mg) tablet at bedtime
(TDF/EFV/3TC) Symfi Lo: Symfi Lo:
Symfi Lo • (TDF 300 mg plus • 1 tablet once daily on an
(TDF/EVG/c/ Stribild: Stribild:
FTC) • (TDF 300 mg plus • 1 tablet once daily
Stribild EVG 150 mg plus • T ake with food.
COBI 150 mg plus
FTC 200 mg) tablet
(TDF/RPV/FTC) Complera: Complera:
Complera • (TDF 300 mg plus • 1 tablet once daily
RPV 25 mg plus •T
ake with a meal.
FTC 200 mg) tablet

Generic Name Serum/
Dosing Elimination/
Zidovudine Retrovir: Retrovir: Metabolized to GAZT 1.1 hours/ • Bone marrow suppression:
(ZDV) • 100 mg capsule • ZDV 300 mg BID, or 7 hours macrocytic anemia or
Retrovir Renal excretion of neutropenia
• 300 mg tablet • ZDV 200 mg TID GAZT
Note: Generic is (only available as • Nausea, vomiting, headache,
• Take without regard to Dose adjustment insomnia, asthenia
available. generic) meals. is recommended in • Nail pigmentation
• 10 mg/mL patients with renal
intravenous insufficiency (see • Lactic acidosis/severe
solution Appendix B, Table 8). hepatomegaly with hepatic
• 10 mg/mL oral steatosis (rare but potentially
solution life-threatening toxicity)
(ZDV/3TC) Combivir: Combivir: • Hyperlipidemia
Combivir • (ZDV 300 mg plus • 1 tablet BID • Insulin resistance/diabetes
3TC 150 mg) tablet • T mellitus
Note: Generic is ake without regard to
available. meals. • Lipoatrophy
(ZDV/3TC/ABC) Trizivir: Trizivir: • Myopathy
Trizivir • (ZDV 300 mg plus • 1 tablet BID
Note: Generic is 3TC 150 mg plus • Take without regard to
available. ABC 300 mg) meals.
tablet
a
For dose adjustments in patients with renal or hepatic insufficiency, see Appendix B, Table 8.
b
Also see Table 15.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; BIC = bictegravir; BID = twice daily; COBI = cobicistat; CrCl = creatinine clearance;
d4T = stavudine; ddI = didanosine; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EC = enteric coated; EFV = efavirenz; EVG
= elvitegravir; FDC = fixed-dose combination; FTC = emtricitabine; GAZT = azidothymidine glucuronide; HBV = hepatitis B virus; HLA =
human leukocyte antigen; HSR = hypersensitivity reaction; MI = myocardial infarction; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF
= tenofovir disoproxil fumarate; TID = three times a day; WHO = World Health Organization; ZDV = zidovudine

Appendix B, Table 2. Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (Last
Note: DLV is not included in this table. Please refer to the DLV Food and Drug Administration package insert for related
information.
Generic Name
Dosing Elimination/Metabolic Serum
(Abbreviation) Formulations Adverse Eventsb
Recommendationsa Pathway Half-Life
Trade Name
Doravirine Pifeltro: Pifeltro: CYP3A4/5 substrate 15 hours • Nausea
(DOR) • 100 mg tablet • 1 tablet once daily • Dizziness
Pifeltro
• Abnormal dreams
(DOR/TDF/3TC) Delstrigo: Delstrigo:
Delstrigo • (DOR 100 mg plus • 1 tablet once daily
TDF 300 mg plus
3TC 300 mg) tablet
Efavirenz Sustiva: Sustiva: Metabolized by CYPs 2B6 40–55 • Rashc
(EFV) • 50 and 200 mg • 600 mg once daily, at or (primary), 3A4, and 2A6 hours • Neuropsychiatric
Sustiva capsules before bedtime symptomsd
CYP3A4 mixed inducer/
Note: Generic • 600 mg tablet • Take on an empty stomach inhibitor (more an inducer • Increased transaminase
product is to reduce side effects. than an inhibitor) CYP2C9 levels
available. Generic: and 2C19 inhibitor; 2B6 • Hyperlipidemia
• 600 mg tablet inducer
• False-positive results with
(EFV/TDF/FTC) Atripla: Atripla: some cannabinoid and
Atripla • (EFV 600 mg plus • 1 tablet once daily on an benzodiazepine screening
TDF 300 mg plus empty stomach, preferably assays reported
FTC 200 mg) tablet at bedtime • QT interval prolongation
(EFV/TDF/3TC) Symfi: Symfi:
Symfi • (EFV 600 mg plus • 1 tablet once daily on an
TDF 300 mg plus empty stomach, preferably
(EFV/TDF/3TC) Symfi Lo: Symfi Lo:
Symfi Lo • (EFV 400 mg plus • 1 tablet once daily on an
TDF 300 mg plus empty stomach, preferably
Etravirine Intelence: Intelence: CYP3A4, 2C9, and 2C19 41 hours • Rash, including Stevens-
(ETR) • 25, 100, and 200 • 200 mg BID substrate Johnson syndromec
Intelence mg tablets • HSRs, characterized
• Take following a meal. 3A4 inducer; 2C9 and
2C19 inhibitor by rash, constitutional
findings, and sometimes
organ dysfunction
(including hepatic failure)
have been reported.
• Nausea

Appendix B, Table 2. Characteristics of Non-Nucleoside Reverse Transcriptase Inhibitors (Last
Generic Name
Recommendationsa Pathway Half-Life
Trade Name
Nevirapine • 2 00 mg tablet • 2 00 mg once daily for CYP450 substrate, 25–30 • Rash, including Stevens-
(NVP) • 4 00 mg XR tablet 14 days (lead-in period); inducer of 3A4 and hours Johnson syndromec
Viramune or thereafter, 200 mg BID, 2B6; 80% excreted in • Symptomatic hepatitis,
Viramune XR • 5 0 mg/5 mL oral or 400 mg (Viramune XR urine (glucuronidated
suspension including fatal hepatic
tablet) once daily metabolites, <5% necrosis, has been
Note: Generic is unchanged); 10% in feces
available for 200 • Take without regard to reported:
mg tablets and meals. Contraindicated in patients • Rash reported in
oral suspension. •R
epeat lead-in period if with moderate to severe approximately 50% of
therapy is discontinued for hepatic impairment. cases.
>7 days. • Occurs at significantly
Dose adjustment is
• In patients who develop higher frequency in
recommended in patients
mild-to-moderate rash ARV-naive female
on hemodialysis (see
without constitutional patients with pre-NVP
Appendix B, Table 8).
symptoms, continue CD4 counts >250 cells/
lead-in period until rash mm3 and in ARV-naive
resolves, but do not male patients with
administer for longer than pre-NVP CD4 counts
28 days total. >400 cells/mm3. NVP
should not be initiated
in these patients unless
the benefit clearly
outweighs the risk.
Rilpivirine Edurant: Edurant: CYP3A4 substrate 50 hours • Rashc
(RPV) • 25 mg tablet • 25 mg once daily • Depression, insomnia,
Edurant headache
• Take with a meal.
(RPV/DTG) Juluca: Juluca: • Hepatotoxicity
Juluca • (RPV 25 mg plus • 1 tablet once daily • QT interval prolongation
DTG 50 mg) tablet • Take with a meal.
(RPV/TAF/FTC) Odefsey: Odefsey:
Odefsey • (RPV 25 mg plus • 1 tablet once daily
TAF 25 mg plus • Take with a meal.
FTC 200 mg) tablet
(RPV/TDF/FTC) Complera: Complera:
Complera • (RPV 25 mg plus • 1 tablet once daily
TDF 300 mg plus • Take with a meal.
FTC 200 mg) tablet
a
For dose adjustments in patients with renal or hepatic insufficiency, see Appendix B, Table 8.
b
Also see Table 15.
c
Rare cases of Stevens-Johnson syndrome have been reported with most NNRTIs; the highest incidence of rash was seen with NVP.
d
dverse events can include dizziness, somnolence, insomnia, abnormal dreams, depression, suicidality (suicide, suicide attempt or
A
ideation), confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria.
Approximately 50% of patients receiving EFV may experience any of these symptoms. Symptoms usually subside spontaneously after 2
to 4 weeks but may necessitate discontinuation of EFV in a small percentage of patients.
Key to Acronyms: 3TC = lamivudine; ARV = antiretroviral; BID = twice daily; CD4 = CD4 T lymphocyte; CYP = cytochrome P; DLV
= delavirdine; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; FTC = emtricitabine; HSR = hypersensitivity
reaction; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF =
tenofovir disoproxil fumarate; XR = extended release

Appendix B, Table 3. Characteristics of Protease Inhibitors (Last updated October 25, 2018; last
reviewed October 25, 2018) (page 1 of 6)
Generic Name
Elimination/Metabolic Serum
(Abbreviation) Formulations Dosing Recommendationsa Adverse Eventsb
Pathway Half-Life
Trade Name
Atazanavir Reyataz: In ARV-Naive Patients: CYP3A4 inhibitor and 7 hours • Indirect hyperbilirubinemia
(ATV) • 150, 200, • (ATV 300 mg plus RTV 100 mg) substrate; weak CYP2C8 • PR interval prolongation:
Reyataz and 300 mg once daily; or inhibitor; UGT1A1 inhibitor First degree symptomatic
Note: Generic capsules • ATV 400 mg once daily Dose adjustment is AV block reported. Use
is available • 50 mg single recommended in patients with caution in patients who
for capsule packet oral With TDF or in ARV-Experienced with hepatic insufficiency have underlying conduction
formulations. powder Patients: (see Appendix B, Table 8). defects or who are on
• (ATV 300 mg plus RTV 100 mg) concomitant medications
once daily that can cause PR
prolongation.
With EFV in ARV-Naive Patients: • Hyperglycemia
• (ATV 400 mg plus RTV 100 mg) • Fat maldistribution
once daily
• Cholelithiasis
Take with food. • Nephrolithiasis
For dosing recommendations with • Renal insufficiency
H2 antagonists and PPIs, refer to • Serum transaminase
Table 19a. elevations
(ATV/c) Evotaz: Evotaz: ATV: as above • Hyperlipidemia (especially
Evotaz • (ATV 300 mg • 1 tablet once daily with RTV boosting)
COBI: CYP3A inhibitor and
plus COBI •T ake with food. substrate; CYP2D6 inhibitor • Skin rash
150 mg)
tablet With TDF: • Increase in serum creatinine
(with COBI)
• Not recommended for patients
with baseline CrCl <70 mL/min
(see Appendix B, Table 8 for the
equation for calculating CrCl).

Generic Name
Pathway Half-Life
Trade Name
Darunavir Prezista: In ARV-Naive Patients or ARV- CYP3A4 inhibitor and 15 hours • Skin rash (10%): DRV
(DRV) • 75, 150, 600, Experienced Patients with No DRV substrate; CYP2C9 inducer (when has a sulfonamide moiety;
Prezista and 800 mg Mutations: combined Stevens-Johnson syndrome,
tablets • (DRV 800 mg plus RTV 100 mg) with RTV) toxic epidermal necrolysis,
once daily acute generalized
• 100 mg/ exanthematous pustulosis,
mL oral In ARV-Experienced Patients with and erythema multiforme
suspension One or More DRV Resistance have been reported.
Mutations: • Hepatotoxicity
• (DRV 600 mg plus RTV 100 mg) • Diarrhea, nausea
BID
• Headache
Unboosted DRV is not • Hyperlipidemia
recommended.
• Serum transaminase
Take with food. elevation
(DRV/c) Prezcobix: Prezcobix: DRV: CYP3A4 inhibitor and 7 hours • Hyperglycemia
Prezcobix • (DRV 800 mg • 1 tablet once daily substrate; CYP2C9 inducer (when •F at maldistribution
plus COBI combined
•T ake with food. COBI: CYP3A inhibitor and with • Increase in serum creatinine
150 mg) substrate; CYP2D6 inhibitor COBI) (with COBI)
tablet Not recommended for patients
with 1 or more DRV resistance-
associated mutations.
With TDF:
• Not recommended for patients
with baseline CrCl <70 mL/min
(see Appendix B, Table 8 for the
equation for calculating CrCl).
(DRV/c/TAF/ Symtuza: Symtuza: DRV: CYP3A4 inhibitor and
FTC) • (DRV 800 mg • 1 tablet once daily with food substrate; CYP2C9 inducer
Symtuza plus COBI
Not recommended for patients COBI: CYP3A inhibitor and
150 mg plus substrate; CYP2D6 inhibitor
TAF 10 mg with 1 or more DRV resistance-
plus FTC 200 associated mutations.
mg) tablet Not recommended for patients
with CrCl <30 mL/min.
Not recommended in patients with
severe hepatic impairment.

Generic Name
Pathway Half-Life
Trade Name
Fosamprenavir Lexiva: In ARV-Naive Patients: APV is a CYP3A4 7.7 hours • Skin rash (reported in 12%
(FPV, a prodrug • 700 mg tablet • FPV 1400 mg BID, or substrate, inhibitor, and (APV) to 19% of patients on FPV):
of APV) inducer. FPV has a sulfonamide
Lexiva • 50 mg/ • (FPV 1400 mg plus RTV 100–200 moiety.
mL oral mg) once daily, or Dose adjustment is
Note: Generic is suspension recommended in patients • Diarrhea, nausea, vomiting
• (FPV 700 mg plus RTV 100 mg)
available. BID with hepatic insufficiency • Headache
(see Appendix B, Table 8). • Hyperlipidemia
In PI-Experienced Patients (Once-
Daily Dosing Not Recommended): • Serum transaminase
elevation
• (FPV 700 mg plus RTV 100 mg)
BID • Hyperglycemia
• Fat maldistribution
With EFV:
• Possible increase in the
• (FPV 700 mg plus RTV 100 mg) frequency of bleeding
BID, or episodes in patients with
• (FPV 1400 mg plus RTV 300 mg) hemophilia
once daily • Nephrolithiasis
Tablet:
• Without RTV tablet: Take without
regard to meals.
• With RTV tablet: Take with meals.
Oral Suspension:
• Take without food.
Indinavir Crixivan: Crixivan: CYP3A4 inhibitor and 1.5–2 • Nephrolithiasis
(IDV) • 200 and 400 • IDV 800 mg every 8 hours substrate hours • GI intolerance, nausea
Crixivan mg capsules • Take 1 hour before or 2 hours Dose adjustment is • Hepatitis
after meals; may take with skim recommended in patients • Indirect hyperbilirubinemia
milk or a low-fat meal. with hepatic insufficiency
(see Appendix B, Table 8). • Hyperlipidemia
With RTV: • Headache, asthenia,
• (IDV 800 mg plus RTV 100–200 blurred vision, dizziness,
mg) BID rash, metallic taste,
• Take without regard to meals. thrombocytopenia, alopecia,
and hemolytic anemia
Drink at least 48 oz of water daily. • Hyperglycemia
frequency of bleeding
episodes in patients with
hemophilia

Generic Name
Pathway Half-Life
Trade Name
Lopinavir/ Kaletra Kaletra: CYP3A4 inhibitor and 5–6 • GI intolerance, nausea,
Ritonavir Tablets: • (LPV 400 mg plus RTV 100 mg) substrate hours vomiting, diarrhea
(LPV/r) • (LPV 200 mg BID, or • Pancreatitis
Kaletra plus RTV 50 • (LPV 800 mg plus RTV 200 mg) • Asthenia
mg), or once daily • Hyperlipidemia (especially
• (LPV 100 mg hypertriglyceridemia)
plus RTV 25 Once-daily dosing is not
mg) recommended for patients with • Serum transaminase
≥3 LPV-associated mutations, elevation
Oral Solution: pregnant women, or patients • Hyperglycemia
• Each 5 mL receiving EFV, NVP, FPV, NFV,
carbamazepine, phenytoin, or • Insulin resistance/diabetes
contains mellitus
(LPV 400 mg phenobarbital.
plus RTV 100 With EFV or NVP (PI-Naive or PI • Fat maldistribution
mg). Experienced Patients): • Possible increase in the
• Oral solution • LPV/r 500 mg/125 mg tablets frequency of bleeding
contains 42% BID (use a combination of 2 episodes in patients with
alcohol. hemophilia
LPV/r 200 mg/50 mg tablets plus
1 LPV/r 100 mg/25 mg tablet to • PR interval prolongation
make a total dose of LPV/r 500 • QT interval prolongation and
mg/125 mg), or torsades de pointes have
• LPV/r 533 mg/133 mg oral been reported; however,
solution BID causality could not be
established.
Tablet:
• Take without regard to meals.
Oral Solution:
• Take with food.
Nelfinavir Viracept: Viracept: CYP2C19 and 3A4 3.5–5 • Diarrhea
(NFV) • 250 and 625 • NFV 1250 mg BID, or substrate—metabolized hours • Hyperlipidemia
Viracept mg tablets to active M8 metabolite;
• NFV 750 mg TID CYP3A4 inhibitor • Hyperglycemia
Dissolve tablets in a small amount • Fat maldistribution
of water, mix admixture well, and • Possible increase in the
consume immediately. frequency of bleeding
Take with food. hemophilia
• Serum transaminase
elevation

Generic Name
Pathway Half-Life
Trade Name
Ritonavir Norvir: As PK Booster (or Enhancer) for CYP3A4 > 2D6 substrate; 3–5 • GI intolerance, nausea,
(RTV) • 100 mg tablet Other PIs: potent 3A4, 2D6 inhibitor; hours vomiting, diarrhea
Norvir inducer of UGT1A1 and
• 100 mg soft • RTV 100–400 mg per day in CYPs 1A2, 2C8, 2C9, and
• Paresthesia (circumoral and
Note: Generic is gel capsule 1 or 2 divided doses (refer to extremities)
other PIs for specific dosing 2C19
available. • 80 mg/mL • Hyperlipidemia (especially
recommendations). hypertriglyceridemia)
oral solution
• 100 mg Tablet: • Hepatitis
single packet • Take with food. • Asthenia
oral powder • Taste perversion
Capsule and Oral Solution:
Oral solution • To improve tolerability, take with • Hyperglycemia
contains 43% food if possible. • Fat maldistribution
alcohol.
hemophilia
Saquinavir Invirase: Invirase: CYP3A4 substrate 1–2 • GI intolerance, nausea, and
(SQV) • 500 mg tablet • (SQV 1000 mg plus RTV 100 mg) hours diarrhea
Invirase BID • Headache
• 200 mg
capsule Unboosted SQV is not • Serum transaminase
recommended. elevation
• Hyperlipidemia
Take with meals or within 2 hours
after a meal. • Hyperglycemia
hemophilia
• PR interval prolongation
• QT interval prolongation,
torsades de pointes have
been reported. Patients with
pre-SQV QT interval >450
msec should not receive
SQV.

Generic Name
Pathway Half-Life
Trade Name
Tipranavir Aptivus: Aptivus: CYP3A4 inducer and 6 hours • Hepatotoxicity: clinical
(TPV) • 250 mg • (TPV 500 mg plus RTV 200 mg) substrate after hepatitis (including
Aptivus capsule BID single hepatic decompensation
CYP2D6 inhibitor; CYP3A4, dose of and hepatitis-associated
• 100 mg/mL Unboosted TPV is not 1A2, and 2C19 inducer TPV/r fatalities) has been reported;
oral solution recommended. monitor patients closely,
Net effect of combining
TPV and RTV is a CYP3A4 especially those with
With RTV Tablets:
and 2D6 inhibitor underlying liver diseases.
• Take with meals. • Skin rash: TPV has a
With RTV Capsules or Solution: sulfonamide moiety; use
with caution in patients with
• Take without regard to meals.
known sulfonamide allergy.
• Rare cases of fatal and
nonfatal intracranial
hemorrhages have been
reported. Risks include brain
lesion, head trauma, recent
neurosurgery, coagulopathy,
hypertension, alcoholism,
and the use of anticoagulant
or antiplatelet agents
(including vitamin E).
• Hyperlipidemia
• Hyperglycemia
hemophilia
a
For dose adjustments in patients with hepatic insufficiency, see Appendix B, Table 8.
b
Also see Table 15.
Key to Acronyms: APV = amprenavir; ARV = antiretroviral; ATV = atazanavir; AV = atrioventricular; BID = twice daily; COBI = cobicistat;
CrCl = creatinine clearance; CYP = cytochrome P; DRV = darunavir; DRV/c = darunavir/cobicistat; EFV = efavirenz; FPV = fosamprenavir;
FTC = emtricitabine; GI = gastrointestinal; IDV = indinavir; LPV = lopinavir; LPV/r = lopinavir/ritonavir; msec = millisecond; NFV = nelfinavir;
NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; PPI = proton pump inhibitor; RTV = ritonavir; SQV = saquinavir; TAF
= tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TID = three times a day; TPV = tipranavir; UGT = uridine diphosphate
glucuronosyltransferase

Appendix B, Table 4. Characteristics of Integrase Inhibitors (Last updated October 25, 2018; last
Generic Name
Recommendationsa Pathways Half-Life
Trade Name
Bictegravir Biktarvy: Biktarvy: BIC: BIC: • Diarrhea
(BIC) • (BIC 50 mg • 1 tablet once daily • CYP3A4 substrate ~17 • Nausea
Note: BIC is plus TAF • UGT1A1 mediated hours • Headache
only available 25 mg plus glucuronidation
as a component FTC 200 mg)
of an FDC. tablet
(BIC/TAF/FTC)
Biktarvy
Dolutegravir Tivicay: In ARV-Naive or ARV- UGT1A1 mediated ~14 • Insomnia
(DTG) • 50 mg tablet Experienced, INSTI-Naive glucuronidation hours • Headache
Tivicay Patients:
Minor contribution from • Depression and suicidal
• 50 mg once daily CYP3A4 ideation (rare; usually in
In ARV-Naive or patients with pre-existing
ARV-Experienced, INSTI- psychiatric conditions)
Naive Patients when • Hepatotoxicity
Coadministered with EFV, • Preliminary data suggest
FPV/r, TPV/r, or Rifampin: increased rate of neural tube
• 50 mg BID defects in infants born to
mothers who were taking DTG
INSTI-Experienced Patients at the time of conception.
with Certain INSTI Mutations
(See Product Label) or with • HSRs, including rash,
Clinically Suspected INSTI constitutional symptoms, and
Resistance: organ dysfunction (including
liver injury) have been
• 50 mg BID reported.
Take without regard to meals.
(DTG/ Triumeq: Triumeq:
ABC/3TC) • (DTG 50 mg • 1 tablet once daily
Triumeq plus ABC
600 mg plus
3TC 300 mg)
tablet
(DTG/RPV) Juluca: Juluca:
Juluca • (DTG 50 mg • 1 tablet once daily with a
plus RPV 25 meal
mg) tablet

Appendix B, Table 4. Characteristics of Integrase Inhibitors (Last updated October 25, 2018; last
Generic Name
Recommendationsa Pathways Half-Life
Trade Name
Elvitegravir N/A N/A N/A N/A • Nausea
(EVG) • Diarrhea
Note: EVG is • Depression and suicidal
only available ideation (rare; usually in
as a component patients with pre-existing
of an FDC. psychiatric conditions)
(EVG/c/FTC/ Genvoya: Genvoya: EVG: CYP3A, UGT1A1/3 ~13
TAF) • (EVG 150 mg • 1 tablet once daily with food substrate hours
Genvoya plus COBI (EVG/c)
Not recommended for COBI: CYP3A inhibitor and
150 mg plus
FTC 200 mg patients with CrCl <30 mL/min substrate; CYP2D6 inhibitor
plus TAF 10 (see Appendix B, Table 8 for
mg) tablet the equation for calculating
CrCl).
Not recommended for use
with other ARV drugs.
(EVG/c/FTC/ Stribild: Stribild:
TDF) • (EVG 150 mg • 1 tablet once daily with food
Stribild plus COBI
150 mg plus Not recommended for
FTC 200 mg patients with baseline CrCl
plus TDF 300 <70 mL/min (see Appendix B,
mg) tablet Table 8 for the equation for
calculating CrCl).
Not recommended for use
with other ARV drugs.
Raltegravir • 4 00 mg tablet In ARV-Naive Patients or UGT1A1-mediated ~9 hours • Rash, including Stevens-
(RAL) • 6 00 mg tablet ARV-Experienced Patients: glucuronidation Johnson syndrome, HSR, and
Isentress (HD) • Isentress: 400 mg BID toxic epidermal necrolysis
Isentress HD • Nausea
• 2 5 and 100 In ARV-Naive or ARV-
mg chewable Experienced Patients with • Headache
tablets Virologic Suppression on a • Diarrhea
• 1 00 mg Regimen of RAL 400 mg BID: • Pyrexia
single packet • Isentress HD: 1200 mg (two
for oral • CPK elevation, muscle
600-mg tablets) once daily weakness, and
suspension
With Rifampin: rhabdomyolysis
• Isentress: 800 mg BID • Insomnia
• Isentress HD: Not • Depression and suicidal
recommended ideation (rare; usually in
patients with pre-existing
Take without regard to meals. psychiatric conditions)
a
For dosage adjustment in patients with hepatic insufficiency, see Appendix B, Table 8.
b
Also see Table 15.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; BIC = bictegravir; BID = twice daily; COBI = cobicistat;
CPK = creatine phosphokinase; CrCl = creatinine clearance; CYP = cytochrome P; DTG = dolutegravir; EFV = efavirenz; EVG =
elvitegravir; EVG/c = elvitegravir/cobicistat; FDC = fixed-dose combination; FPV/r = fosamprenavir/ritonavir; FTC = emtricitabine; HSR =
hypersensitivity reaction; INSTI = integrase strand transfer inhibitor; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF
= tenofovir disoproxil fumarate; TPV/r = tipranavir/ritonavir; UGT = uridine diphosphate gluconyltransferase

Appendix B, Table 5. Characteristics of the Fusion Inhibitor (Last updated January 29, 2008; last
reviewed October 25, 2018)
Generic Name
Dosing Serum
(Abbreviation) Formulation Elimination Adverse Eventsa
Recommendation Half-Life
Trade Name
Enfuvirtide Fuzeon: Fuzeon: 3.8 hours Expected to undergo • Local injection site reactions (e.g.,
(T-20) • Injectable; supplied as • 90 mg (1 mL) catabolism to its pain, erythema, induration, nodules
Fuzeon lyophilized powder subcutaneously constituent amino and cysts, pruritus, ecchymosis)
BID acids, with subsequent occur in almost 100% of patients
• Each vial contains recycling of the amino
108 mg of T-20; • Increased incidence of bacterial
acids in the body pool pneumonia
reconstitute with 1.1
mL of sterile water for • HSR (<1% of patients). Symptoms
injection for delivery may include rash, fever,
of approximately 90 nausea, vomiting, chills, rigors,
mg/1 mL. hypotension, or elevated serum
• Refer to prescribing transaminases. Rechallenge is
information for storage not recommended.
instruction.
a
Also see Table 15.
Key to Abbreviations: BID = twice daily; HSR = hypersensitivity reaction; T-20 = enfuvirtide
Appendix B, Table 6. Characteristics of CCR5 Antagonist (Last updated March 27, 2012; last
reviewed October 25, 2018)
Generic Name
Dosing Serum Half- Elimination/
(Abbreviation) Formulation Adverse Eventsb
Recommendationsa Life Metabolic Pathway
Trade Name
Maraviroc Selzentry: Selzentry: 14–18 hours CYP3A4 substrate • Abdominal pain
(MVC) • 150 and 300 • 150 mg BID when given • Cough
Selzentry mg tablets with drugs that are strong • Dizziness
CYP3A inhibitors (with or
without CYP3A inducers), • Musculoskeletal symptoms
including PIs (except • Pyrexia
TPV/r) • Rash
• 300 mg BID when given • Upper respiratory tract
with NRTIs, T-20, TPV/r, infections
NVP, RAL, and other
• Hepatotoxicity, which may be
drugs that are not strong
preceded by severe rash or
CYP3A inhibitors or
other signs of systemic allergic
inducers
reactions
• 600 mg BID when given
• Orthostatic hypotension,
with drugs that are CYP3A
especially in patients with
inducers, including EFV,
severe renal insufficiency
ETR, etc. (without a
CYP3A inhibitor)
Take without regard to
meals.
a
For dosage adjustment in hepatic insufficiency, see Appendix B, Table 8.
b
Also see Table 15.
Key to Acronyms: BID = twice daily; CYP = cytochrome P; EFV = efavirenz; ETR = etravirine; MVC = maraviroc; NRTI = nucleoside
reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; RAL = raltegravir; T-20 = enfuvirtide; TPV/r = tipranavir/ritonavir

Appendix B, Table 7. Characteristics of CD4 Post-Attachment Inhibitor (Last updated October 25,
2018; last reviewed October 25, 2018)
Generic Name
Serum Elimination/ Metabolic
(Abbreviation) Formulation Dosing Recommendations Adverse Events
Half-Life Pathway
Trade Name
Ibalizumab Trogarzo: Trogarzo: ~64 hours Not well defined. • Diarrhea
(IBA) • Single-dose • Administer a single loading • Dizziness
Trogarzo 2 mL vial dose of IBA 2000 mg IV • Nausea
containing 200 infusion over 30 minutes,
mg/1.33 mL followed by a maintenance • Rash
(150 mg/mL) of dose of IBA 800 mg IV
ibalizumab infusion over 15 minutes
every 2 weeks.
• See prescribing information
for additional instruction
in preparation, storage,
administration, and
monitoring.
Key to Acronyms: IBA = ibalizumab; IV = intravenous

Appendix B, Table 8. Antiretroviral Dosing Recommendations in Patients with Renal or Hepatic
Insufficiency (Last updated October 25, 2018; last reviewed October 25, 2018) (page 1 of 7)
See the reference section at the end of this table for CrCl calculation formulas and criteria for Child-Pugh
classification.
ARVs
Generic Name Dosing in Patients with Renal Dosing in Patients with Hepatic
Usual Daily Dosea
(Abbreviation) Insufficiencyb Impairment
Trade Name
NRTIs
Stribild should not be initiated in patients with CrCl <70 mL/min. The following FDCs are not recommended in patients with CrCl <50 mL/
min: Atripla, Combivir, Complera, Delstrigo, Epzicom, Triumeq, or Trizivir. Biktarvy, Descovy, Genvoya, Odefsey, Symtuza, and Truvada
are not recommended in patients with CrCl <30 mL/min.
Abacavir • 300 mg PO BID, or No dose adjustment necessary. Child-Pugh Class A:
(ABC) • 600 mg PO once daily • 200 mg PO BID (use oral solution)
Ziagen
Child-Pugh Class B or C:
• Contraindicated
Didanosine EC Body Weight ≥60 kg: Once-Daily Dose by Body Weight No dose adjustment necessary.
(ddI) • 400 mg PO once daily CrCl (mL/min) ≥60 kg <60 kg
Videx EC
Body Weight <60 kg: 30–59 200 mg 125 mg
• 250 mg PO once daily 10–29 125 mg 125 mg
<10, HD, or
c
125 mg 75 mg oral
CAPD solution
Didanosine Oral Body Weight ≥60 kg: Once-Daily Dose by Body Weight No dose adjustment necessary.
Solution • 200 mg PO BID, or
(ddI) CrCl (mL/min) ≥60 kg <60 kg
Videx • 4
00 mg PO once daily 30–59 200 mg 150 mg
Body Weight <60 kg: 10–29 150 mg 100 mg
• 250 mg PO once daily, or <10, HD, or
c
100 mg 75 mg
• 125 mg PO BID CAPD
Emtricitabine • 2 00 mg oral capsule once Dose No dose recommendation.
(FTC) daily, or CrCl (mL/
Emtriva • 2 40 mg (24 mL) oral Capsule Solution
min)
solution once daily 30–49 200 mg q48h 120 mg q24h
15–29 200 mg q72h 80 mg q24h
<15 or on 200 mg q96h 60 mg q24h
HDc
Lamivudine • 3 00 mg PO once daily, or CrCl (mL/ No dose adjustment necessary.
Dose
(3TC) • 1 50 mg PO BID min)
Epivir 30–49 150 mg q24h
15–29 1 x 150 mg, then 100 mg q24h
5–14 1 x 150 mg, then 50 mg q24h
<5 or on 1 x 50 mg, then 25 mg q24h
HDc
Stavudine Body Weight ≥60 kg: Dose No dose recommendation
(d4T) • 40 mg PO BID CrCl (mL/min) ≥60 kg <60 kg
Zerit
Body Weight <60 kg: 26–50 20 mg 15 mg q12h
q12h
• 30 mg PO BID
10–25 or on HDc 20 mg 15 mg q24h
q24h

ARVs
Usual Daily Dosea
Trade Name
NRTIs, continued
Tenofovir • TAF for HIV treatment CrCl (ml/min) Dose Child-Pugh Class A or B:
Alafenamide/ is only available as a <30 or on HD c
Not recommended • No dose adjustment
Emtricitabine component of FDCs
(TAF/FTC) (i.e., Descovy, Genvoya, Child-Pugh Class C:
Descovy Odefsey, Biktarvy, and • No dose recommendation
Symtuza).
• TAF 10 mg PO daily with
EVG/c (Genvoya) or
DRV/c (Symtuza)
• TAF 25 mg PO daily in
other FDCs
Tenofovir Disoproxil • 300 mg PO once daily CrCl (mL/min) Dose No dose adjustment necessary.
Fumarate 30–49 300 mg q48h
(TDF)
Viread 10–29 300 mg twice weekly
(every 72–96 hours)
<10 and not on HD No recommendation
On HDc 300 mg q7d
Tenofovir Disoproxil • 1 tablet PO once daily CrCl (mL/min) Dose No dose recommendation.
Fumarate/Emtricitabine
30–49 1 tablet q48h
(TDF/FTC)
Truvada <30 or on HD Not recommended
Tenofovir Disoproxil • 1 tablet PO once daily CrCl (mL/min) Dose No dose recommendation.
Fumarate/Lamivudine
<50 or on HD Not recommended
(TDF/3TC)
Cimduo
Zidovudine • 300 mg PO BID CrCl (mL/min) Dose No dose recommendation.
(ZDV) <15 or on HD c
100 mg TID or 300
Retrovir mg once daily
NNRTIs
Doravirine • 1 tablet PO once daily No dose adjustment required in mild, Child-Pugh Class A or B:
(DOR) moderate, or severe renal impairment. Has • No dose adjustment
Pifeltro not been studied in ESRD or HD.
Child-Pugh Class C:
• Not studied
Doravine/Tenofovir • 1 tablet PO once daily Not recommended if CrCl <50 mL/min. Child-Pugh Class A or B:
Disoproxil Fumarate/ • No dose adjustment
Lamivudine
(DOR/TDF/3TC) Child-Pugh Class C:
Delstrigo • Not studied
Efavirenz • 600 mg PO once daily, No dose adjustment necessary. No dose recommendation; use with
(EFV) on an empty stomach, caution in patients with hepatic
Sustiva preferably at bedtime impairment.
Efavirenz/Tenofovir • 1 tablet once daily on Not recommended if CrCl <50 mL/min. No dose recommendation; use with
Disoproxil Fumarate/ an empty stomach, Instead, use the individual drugs and caution in patients with hepatic
Emtricitabine preferably at bedtime adjust TDF and FTC doses according to impairment.
(EFV/TDF/FTC) CrCl level.
Atripla

ARVs
Usual Daily Dosea
Trade Name
Efavirenz 600 mg/ • 1 tablet once daily on Not recommended if CrCl <50 mL/min or if Not recommended for patients
Tenofovir Disoproxil an empty stomach, patient is on HD. Instead, use the individual with moderate or severe hepatic
Fumarate/Lamivudine preferably at bedtime drugs and adjust TDF and 3TC doses impairment. Use caution in patients
(EFV/TDF/3TC) according to CrCl level. with mild hepatic impairment.
Symfi
Efavirenz 400 mg/ • 1 tablet once daily on Not recommended if CrCl <50 mL/min or if Not recommended for patients
Tenofovir Disoproxil an empty stomach, patient is on HD. Instead, use the individual with moderate or severe hepatic
Fumarate/Lamivudine preferably at bedtime drugs and adjust TDF and 3TC doses impairment. Use caution in patients
(EFV/TDF/3TC) according to CrCl level. with mild hepatic impairment.
Symfi Lo
Etravirine • 200 mg PO BID No dose adjustment necessary. Child-Pugh Class A or B:
(ETR) • No dose adjustment
Intelence
Child-Pugh Class C:
• No dose recommendation
Nevirapine • 200 mg PO BID, or No dose adjustment for patients with renal Child-Pugh Class A:
(NVP) • 400 mg PO once daily impairment. • No dose adjustment
Viramune (using Viramune XR Patients on HD should receive an Child-Pugh Class B or C:
or formulation) additional dose of 200 mg following each • Contraindicated
Viramune XR dialysis treatment.
Rilpivirine • 25 mg PO once daily No dose adjustment necessary. Child-Pugh Class A or B:
(RPV) • No dose adjustment
Edurant
Child-Pugh Class C:
Rilpivirine/Tenofovir • 1 tablet PO once daily Not recommended if CrCl <30 mL/min. Child-Pugh Class A or B:
Alafenamide/ • No dose adjustment
Emtricitabine
(RPV/TAF/FTC) Child-Pugh Class C:
Odefsey • No dose recommendation
Rilpivirine/Tenofovir • 1 tablet PO once daily Not recommended if CrCl <50 mL/min. Child-Pugh Class A or B:
Disoproxil Fumarate/ Instead, use the individual drugs and • No dose adjustment
Emtricitabine adjust TDF and FTC doses according to
(RPV/TDF/FTC) CrCl level. Child-Pugh Class C:
Complera • No dose recommendation
Rilpivirine/ • 1 tablet PO once daily No dose adjustment necessary. Child-Pugh Class A or B:
Dolutegravir with food • No dose adjustment
(RPV/DTG) In patients with CrCl <30 mL/min, monitor
Juluca closely for adverse effects. Child-Pugh Class C:
PIs
Atazanavir • 400 mg PO once daily, or No dose adjustment for patients with renal Child-Pugh Class B:
(ATV) • (ATV 300 mg plus RTV dysfunction who do not require HD. • 300 mg once daily (unboosted) for
Reyataz 100 mg) PO once daily ARV-naive patients only
In ARV-Naive Patients on HD:
• (ATV 300 mg plus RTV 100 mg) once daily Child-Pugh Class C:
In ARV-Experienced Patients on HD: • Not recommended
• ATV or ATV/r not recommended RTV boosting is not recommended
in patients with hepatic impairment.

ARVs
Usual Daily Dosea
Trade Name
PIs, continued
Atazanavir/Cobicistat • 1 tablet PO once daily If Used with TDF: Not recommended in patients with
(ATV/c) • Not recommended if CrCl <70 mL/min hepatic impairment.
Evotaz
Darunavir In ARV-Naive Patients and No dose adjustment necessary. In Patients with Mild-to-Moderate
(DRV) ARV-Experienced Patients Hepatic Impairment:
Prezista with No DRV Resistance • No dose adjustment
Mutations:
• (DRV 800 mg plus RTV In Patients with Severe Hepatic
100 mg) PO once daily Impairment:
with food • Not recommended
In ARV-Experienced
Patients with at Least 1
DRV Resistance Mutation:
• (DRV 600 mg plus RTV
100 mg) PO BID
Darunavir/Cobicistat • 1 tablet PO once daily If Used with TDF: Child-Pugh Class A or B:
(DRV/c) • Not recommended if CrCl <70 mL/min • No dose adjustment
Prezcobix
Child-Pugh Class C:
• Not recommended
Darunavir/ • 1 tablet PO once daily Not recommended if CrCl <30 mL/min. Not recommended for patients with
Cobicistat/Tenofovir severe hepatic impairment.
Alafenamide/
Emtricitabine
(DRV/c/TAF/FTC)
Symtuza
Fosamprenavir • 1400 mg PO BID, or No dose adjustment necessary. In PI-Naive Patients Only
(FPV) • (FPV 1400 mg plus RTV Child-Pugh Score 5–9:
Lexiva 100–200 mg) PO once • 700 mg BID
daily, or
• (FPV 700 mg plus RTV Child-Pugh Score 10–15:
100 mg) PO BID • 350 mg BID
In PI-Naive or PI-Experienced
Patients
Child-Pugh Score 5–6:
• (FPV 700 mg BID plus RTV 100
mg) once daily
mg) once daily
mg) once daily

ARVs
Usual Daily Dosea
Trade Name
PIs, continued
Indinavir • 800 mg PO q8h No dose adjustment necessary. In Patients with Mild-to-Moderate
(IDV) Hepatic Insufficiency Due to
Crixivan Cirrhosis:
• 600 mg q8h
Lopinavir/Ritonavir • (LPV 400 mg plus RTV Avoid once-daily dosing in patients on HD. No dose recommendation; use with
(LPV/r) 100 mg) PO BID, or caution in patients with hepatic
Kaletra • (LPV 800 mg plus RTV impairment.
200 mg) PO once daily
Nelfinavir • 1250 mg PO BID No dose adjustment necessary. In Patients with Mild Hepatic
(NFV) Impairment:
Viracept • No dose adjustment
In Patients with Moderate-to-Severe
Hepatic Impairment:
• Not recommended
Ritonavir As a PI-Boosting Agent: No dose adjustment necessary. Refer to recommendations for the
(RTV) • 100–400 mg per day primary PI.
Norvir
Saquinavir • (SQV 1000 mg plus RTV No dose adjustment necessary. In Patients with Mild-to-Moderate
(SQV) 100 mg) PO BID Hepatic Impairment:
Invirase • Use with caution
In Patients with Severe Hepatic
Impairment:
• Contraindicated
Tipranavir • (TPV 500 mg plus RTV No dose adjustment necessary. Child-Pugh Class A:
(TPV) 200 mg) PO BID • Use with caution
Aptivus
• Contraindicated
INSTIs
Bictegravir/Tenofovir • 1 tablet once daily Not recommended for use in patients with Child-Pugh Class C:
Alafenamide/ CrCl <30 mL/min. • Not recommended
Emtricitabine
(BIC/TAF/FTC)
Biktarvy
Dolutegravir • 50 mg once daily, or No dose adjustment necessary. Child-Pugh Class A or B:
(DTG) • 50 mg BID • No dose adjustment
Tivicay
Child-Pugh Class C:
• Not recommended

ARVs
Usual Daily Dosea
Trade Name
INSTIs, continued
Dolutegravir/Abacavir/ • 1 tablet once daily Not recommended if CrCl <50 mL/min. Child-Pugh Class A:
Lamivudine Instead, use the individual drugs and adjust • Patients with mild hepatic
(DTG/ABC/3TC) 3TC dose according to CrCl. impairment require a dose
Triumeq reduction of ABC. Use the
individual drugs instead of the
fixed-dose combination in these
patients.
• Contraindicated, due to the ABC
component
Dolutegravir/ • 1 tablet PO once daily No dose adjustment necessary. Child-Pugh Class A or B:
Rilpivirine with food • No dose adjustment
(DTG/RPV) In patients with CrCl <30 mL/min, monitor
Juluca closely for adverse effects. Child-Pugh Class C:
Elvitegravir/ • 1 tablet once daily Not recommended for use in patients with In Patients with Mild-to-Moderate
Cobicistat/Tenofovir CrCl <30 mL/min. Hepatic Insufficiency:
Alafenamide/ • No dose adjustment necessary
Emtricitabine
(EVG/c/TAF/FTC) In Patients with Severe Hepatic
Genvoya Insufficiency:
• Not recommended
Elvitegravir/ • 1 tablet once daily EVG/c/TDF/FTC should not be initiated In Patients with Mild-to-Moderate
Cobicistat/Tenofovir in patients with CrCl <70 mL/min. Hepatic Insufficiency:
Disoproxil Fumarate/ • No dose adjustment necessary
Emtricitabine Discontinue EVG/c/TDF/FTC if CrCl
(EVG/c/TDF/FTC) declines to <50 mL/min while patient is on In Patients with Severe Hepatic
Stribild therapy. Insufficiency:
• Not recommended
Raltegravir • 400 mg BID (using No dose adjustment necessary. In Patients with Mild-to-Moderate
(RAL) Isentress formulation), or Hepatic Insufficiency:
Isentress • 1200 mg once daily (use • No dose adjustment necessary
Isentress HD Isentress HD formulation
only) In Patients with Severe Hepatic
Insufficiency:
• No recommendation
Fusion Inhibitor
Enfuvirtide • 90 mg subcutaneous BID No dose adjustment necessary. No dose adjustment necessary.
(T-20)
Fuzeon

ARVs
Usual Daily Dosea
Trade Name
CCR5 Antagonist
Maraviroc • The recommended In Patients with CrCl <30 mL/min or No dose recommendations.
(MVC) dose differs based on Patients Who Are on HD MVC concentrations will likely be
Selzentry concomitant medications Without Potent CYP3A Inhibitors or increased in patients with hepatic
and potential for drug- Inducers: impairment.
drug interactions. See
Appendix B, Table 6 • 300 mg BID; reduce to 150 mg BID if
for detailed dosing postural hypotension occurs
information. With Potent CYP3A Inducers or Inhibitors:
• Not recommended
CD4 Post-Attachment Inhibitor
Ibalizumab • Loading dose of 2000 No dose adjustment recommended. No recommendation.
(IBA) mg IV, followed by a
Trogarzo maintenance dose of 800
mg IV every 2 weeks
a
Refer to Appendix B, Tables 1–7 for additional dosing information.
b
Including patients who are on CAPD and HD.
c
On dialysis days, take dose after HD session.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r
= atazanavir/ritonavir; AZT = zidovudine; BIC = bictegravir; BID = twice daily; CAPD = chronic ambulatory peritoneal dialysis; COBI =
cobicistat; CrCl = creatinine clearance; CYP = cytochrome P; d4T = stavudine; ddI = didanosine; DLV = delavirdine; DRV = darunavir;
DRV/c = darunavir/cobicistat; DTG = dolutegravir; DOR = doravirine; EC = enteric coated; EFV = efavirenz; ESRD = end stage renal
disease; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FDC = fixed-dose combination; FPV = fosamprenavir; FTC
= emtricitabine; HD = hemodialysis; IBA = ibalizumab; IDV = indinavir; INSTI = integrase strand transfer inhibitor; IV=intravenous; LPV =
lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NFV = nelfinavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI
= nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PO = orally; q(n)d = every (n) days; q(n)h = every
(n) hours; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF =
tenofovir disoproxil fumarate; TID = three times daily; TPV = tipranavir; XR = extended release; ZDV = zidovudine

Creatinine Clearance Calculation
Male: (140 − age in years) x (weight in kg) Female: (140 − age in years) x (weight in kg) x (0.85)
72 x (serum creatinine) 72 x (serum creatinine)
Child-Pugh Score
Points Scored
Component
1 2 3
a
Encephalopathy None Grade 1–2 Grade 3–4
Ascites None Mild or controlled by diuretics Moderate or refractory
despite diuretics
Albumin >3.5 g/dL 2.8–3.5 g/dL <2.8 g/dL
Total bilirubin or <2 mg/dL (<34 μmol/L) 2–3 mg/dL (34 μmol/L–50 μmol/L) >3 mg/dL (>50 μmol/L)
b
Modified total bilirubin <4 mg/dL 4–7 mg/dL >7 mg/dL
Prothrombin time (seconds prolonged) or <4 4–6 >6
International normalized ratio (INR) <1.7 1.7–2.3 >2.3
a
Encephalopathy Grades
Grade 1: Mild confusion, anxiety, restlessness, fine tremor, slowed coordination
Grade 2: Drowsiness, disorientation, asterixis
Grade 3: Somnolent but rousable, marked confusion, incomprehensible speech, incontinence, hyperventilation
Grade 4: Coma, decerebrate posturing, flaccidity
b
Modified total bilirubin used for patients who have Gilbert’s syndrome or who are taking indinavir or atazanavir
Child-Pugh Classification Total Child-Pugh Scorea

Class A 5–6 points
Class B 7–9 points
Class C >9 points
a
Sum of points for each component of the Child-Pugh Score

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Guidelines for the Use of Antiretroviral Agents in

Adults and Adolescents Living with HIV

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Visit the AIDSinfo website to access the most up-to-date guideline.

Register for e-mail notification of guideline updates at https://aidsinfo.nih.gov/e-news.

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Strength of Recommendationi Quality of Evidence for Recommendation

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Clinical Scenario Viral Load Monitoring CD4 Count Monitoring

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Rating of Recommendations: A = Strong; B = Moderate; C = Optional

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Suspicion of Acute HIV-1 Infection:

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HCV Direct-Acting Antiviral Agents

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TAF: Associated with smaller

Patients should not be A 2-week dose escalation of NVP

ARV Agent(s) or Drug Class

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ARV Drug Tablets, Capsules, or WAC AWP FUL

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Lumefantrine AUC ↑ 2.5-fold

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