Diagnosis and Initial Management of

HIV/AIDS:
What the Primary Care Provider Should Know
 François-Xavier Bagnoud Center

Objectives
• Describe two ways HIV can be transmitted
• Identify two laboratory tests used to assess HIV disease
• Describe the clinical progression of HIV
• Discuss the purpose of antiretroviral treatment

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What is HIV

• Human
• Immunodeficiency
• Virus
• HIV is a retrovirus that attacks the immune system.
• Its genetic material, RNA, must be converted in to DNA
during replication.
• Over time, the immune system and the body loses its ability
to fight the virus.

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HIV and the Immune System

• The CD4 cells coordinate a body’s
immune response to an invader
(bacteria, virus, etc.)

• BUT, when HIV enters CD4 cells for

reproduction, it damages the CD4 cell,
eventually killing it.

• The body’s immune system works hard

making more CD4 cells

• Overtime, HIV destroys the CD4 cells

faster than the immune system can make
new ones

• So, HIV damages the very system that

usually protects the body from infection.

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HIV Life Cycle

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HIV in New Jersey

• 36,648 people are living with HIV

34%
Women
(53%
78%
between
Minorities 20-49)
159
perinatal
79% exposures
40 years 3%
infected
or older

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HIV Transmission
• Blood • Comes into contact
• Semen with:
• Vaginal Secretions – mucous membranes,
damaged tissue, or is
• Breast milk injected into the body
• Through:
– Vaginal, anal, or oral
sex
– Contaminated needles
– IV drug use

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HIV Transmission

• Perinatal transmission during pregnancy, labor and deliver, or

breastfeeding
• Occupational exposure via needle stick or exposure to eyes,
nose, or open wound
– Since 1981 there have been 57 documented cases of occupational
transmission in the US
• Blood transfusion or organ donation from an HIV infected
donor (rare in US)

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HIV Transmission

• HIV is NOT transmitted by casual contact

– Working or playing with an HIV positive person
– Closed mouth kissing
– Shaking hands
– Public pools
– Hugging
– Public toilet
• HIV is not transmitted by air, food, or mosquito and does not
survive long outside the body.

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HIV Testing

• CDC recommends routine HIV testing for ALL patients:

• Aged 13-64
• Initiating TB treatment
• Seeking treatment for STI’s
• Who are pregnant
• Repeat Screening Recommended
• Annually people at high risk
• Before beginning a new sexual relationship
• When clinically indicated
• After an occupational exposure

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HIV Testing

• Benefits of routine opt-out HIV testing

– Reduces the stigma of testing
– Reduces transmission
– Majority of people aware of their HIV status reduce behaviors that
transmit infection
– Perinatal transmission can be prevented if mother’s HIV status is
known
– Improves patient outcomes (with early diagnosis of HIV)

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Sequence of HIV Assay Reactivity During Early HIV
Infection relative to Western Blot*

WB POSITIVE
-25 -20 - 15 -10 -5 0

NAT 4th gen IA 3rd gen Lab IA 2nd gen IA 3rd gen POC IA 1st gen WB

Estimated # of days HIV assay is reactive before a positive Western blot result is obtained
*Assay sensitivity above is based on frozen plasma only. Whole-blood and oral fluid has not been
characterized for early infection.
**Current data suggests that the Gen-Probe Aptima can detect HIV-1 RNA ~9-11 days after
infection.
NY/NJ AETC LPS
Adapted from Owen et al J Clin Micro 2008 and Masciotra et al J Clin Virol 2011
 François-Xavier Bagnoud Center

HIV Laboratory Tests – CD4 Count

• CD4 count –measures
state of a person’s
immune function
– Adult values are
approximately 500-1300
– Used to determine stage
of HIV progression
– Determines risk of
opportunistic infection
– Historically guided
decisions about
antiretroviral therapy
(ART)

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HIV Laboratory Tests – Viral Load

• Detects the amount of virus present

• High viral loads increase risk for disease progression and HIV
transmission
• Monitors effectiveness of ART
• Goal of therapy is an undetectable viral load
• Used during acute infection to detect virus
• Measured by HIV-1 RNA PCR

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Clinical Progression
• Acute Retroviral Syndrome
– Two thirds of all patients experience symptoms
– Occurs 2-6 weeks after initial infection
– Symptoms last 2-4 weeks
– May be mistaken for influenza, mononucleosis, or other viral process
– During this period HIV virus is replicating rapidly and CD4 count
decreases until the body’s immune response recovers CD4 cells and
decreases viral load

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Clinical Progression
• Clinical Latency
– Virus is replicating at low levels
– CD4 cells are maintained at a healthy level
– Virus is transmittable
– This period may last for several years

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Clinical Progression

• Clinical symptoms will begin to develop at the end of this

period as CD4 count falls and viral load increases.
• May include
– Bacillary angiomatosis (lesion on skin caused by infection with gram
negative organism
– Persistent or resistant vulvovaginal candidiasis
– PID
– Cervical Dysplasia
– Hairy leukoplakia
– Herpes Zoster
– Fever or diarrhea lasting longer than one month

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AIDS
• AIDS is characterized by certain infections that take
advantage of the body’s weakened immune system.
• A diagnosis of AIDS is made when an HIV positive patient
has a CD4 count of less that 200 or 14% or the patient is
diagnosed with an AIDS defining condition
• Progression from initial infection with HIV to advanced
HIV/AIDS varies among people and can take several months
to up to 10 years or more.

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Opportunistic Infections

• Opportunistic infections are infections that take advantage of

a weakened immune system to cause more frequent or
severe illness
• CDC identifies 29 infections
• Prophylactic drugs may be given to prevent illness for some
conditions
• Other clinical options include
• Effective ART
• Vaccination
• Avoiding exposure to certain pathogens
• Disease treatment
• Preventing disease recurrence (secondary prophylaxis or chronic
maintenance therapy)
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Clinical Progression

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What can we do?

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Antiretroviral Therapy
• Recommended for all HIV-positive people
• To prevent disease progression
• To prevent transmission of infections
• Strength of recommendation based on
• CD4 count
• Transmission risk

• See Guidelines for the Use of Antiretroviral Agents

in HIV-1 Infected Adults and Adolescents available
at http://www.aidsinfo.nih.gov/ for more info

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Confusing terminology?

• ART = Anti Retroviral Therapy

• ARV = Anti Retro Virals
• HAART = Highly Active Anti Retroviral
Therapy
• Triple Therapy = Three Antiretrovirals
• “The Cocktail”

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Basic Facts about ARVs

• ARVs are divided into • Always use 3 or more

classes, each of which different ARV medications
attacks HIV in a for therapy.
different way. • Regimen should be
• New classes becoming selected by an experienced
available through HCW.
clinical trials. • Other medications interact
with ARVs.

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HIV as a Chronic Disease

ARVs change HIV from a terminal (fatal) disease to a

“chronic disease”

Examples of chronic diseases:

– Diabetes
– High blood pressure
– Asthma
– Schizophrenia

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Advantages of ARV Therapy

• Improved patient
CD4 Count
health
• Reduced illness
• Reduced
hospitalisations Viral Load

• Fewer deaths Time

from AIDS

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Goals of Treatment
• Improve quality of life
• Reduce HIV-related morbidity and mortality
• Restore and/or preserve immunologic
function
• Maximally and durably suppress HIV viral
load
• Prevent HIV transmission

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How do ARVs control HIV?

• ARVs reduce the

ability of the HIV virus HIV
to replicate Replication

• In turn, this increases

the ability of the body
to fight disease Immune

Response
• Reduces the risk of
HIV transmission
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 François-Xavier Bagnoud Center

The Ideal ARV

No toxicities

Good
tolerability

Complete viral
suppression No resistance

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Initial Treatment: Choosing Regimens

• 3 main categories:
– 1 NNRTI + 2 NRTIs
– 1 PI + 2 NRTIs
– 1 II + 2 NRTIs
• Combination of NNRTI, PI, or II + 2 NRTIs preferred
for most patients
• Fusion inhibitor, CCR5 antagonist not
recommended in initial ART
• Advantages and disadvantages to each
type of regimen
• Individualize regimen choice

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Achievable…..?
YES
ARVs are able to significantly reduce viral load,
allowing the immune system to recover followed
by an increase in quality of life and reduction in
morbidity and mortality

BUT

they are not perfect……….

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Managing Side Effects

‘Acceptable’
(transient,
manageable) …..but, ALL must be
reported so that they
Versus can be managed
appropriately
‘Unacceptable’
(severe, adverse
reactions)
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Basic Facts about Adherence and

ARV Therapy
• ARV blood concentrations must remain constant; low
concentrations allow HIV to mutate.

• HIV mutations cause drug resistance.

• ARV medications must be taken every day otherwise they

will not work.

• Things that can lower drug concentrations:

– Missing 1 or 2 ARV medication doses regularly
– Taking ARV medication late
– Taking ARVs with certain foods or other medications

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Treatment Adherence
• A patient’s ability to follow a prescribed treatment
regimen
• Major factor in success of drug regimen
• Significant determinant of survival
• Willingness to start treatment and take medications
exactly as directed
• Level of adherence affects how well ART decreases the
HIV viral load
• Average US ART adherence rate is about 70%

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Treatment Adherence
• Factors associated with poor adherence
– Depression
– Active alcohol or drug use
– Low literacy
– Lack of social support (unstable social situation, chaotic lifestyle)
– Lack of support from partner
– Advance HIV infection
– Young age
– Disbelief in treatment efficacy
– Unstable housing
– Cognitive impairment
– Competing priorities
• Childcare, food and work

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Treatment Adherence
• Complexity of medication regimen
• Adverse drug effects
• Poor patient provider relationships
• Lack of resources
• Poor literacy
• Substance abuse
• Stigma
• Travel away from home
• Sleeping through doses
• Treatment fatigue
– Adherence should be assessed at each visit

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Treatment Adherence
• Strategies to improve adherence
– Choose once daily dosing if possible
– Avoid complex or poorly tolerated regimes
– Use fixed dose combinations if possible
– Use multidisciplinary approach
– Provide tools and support
• Reminder alarms
• Text message reminders
• Education and counseling
• Pill boxes

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Resistance
• Skipping doses of medications may cause the virus to
mutate leading to strains of HIV that are resistant to
medications

• Drug resistant strains can be transmitted

• Viral fitness: Ability of a virus to enter and destroy CD4 cell

(caused by the number resistant mutations developed)

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Resistance Testing
• Genotype
– Amplifies and sequences HIV to look for mutations known to correlate
with drug resistance. Most successful if viral load is above 1000
copies/ml
– Recommended as initial form of resistance testing
• Use to select effective ART
• Phenotype
– HIV reverse transcriptase and protease genes are spliced and created
into a laboratory strain
– The strain is grown in the presence of escalating concentrations of
ARV drugs
• Process takes 2-3 weeks and is costly
– Recommended for patients with complicated multidrug resistance
patterns

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Take Home Messages: HIV 101

• HIV infection is a treatable, chronic illness
• Routine HIV testing is essential not only for treatment of HIV
but also for prevention
• ART improves quality of life and decreases
– Mortality
– Morbidity
– Risk of transmission to partners
• Adherence is key to ARV effectiveness

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Resources

• AIDS Education and Training Center National Resource

Center www.aidsetc.org
• NY/NJ AETC http://www.nynjaetc.org/index.html
• NY/NJ AETC Trainings On-Demand Online Courses
http://www.nynjaetc.org/on-demand/index.html#CME
• National Clinicians Consultation Center www.nccc.ucsf.edu
• AIDSInfo Clinical Guidelines http://aidsinfo.nih.gov/guidelines
• François-Xavier Bagnoud Center http://fxbcenter.org/

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THANK YOU!

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