The item below the virus name are the receptors for the virus on the surface of the

target cells
HIVRead WHO staging

PneumocystisPneumonia (Last updated September 10, 2015; last reviewed September 10, 2015)

Epidemiology Pneumocystis pneumonia(PCP) is caused by Pneumocystis jirovecii, a ubiquitous organism

that is classified as a fungus but also shares biologic characteristics with protozoa. The taxonomy of the
organism has been changed; Pneumocystis cariniinow refers only to the Pneumocystisthat infects rats,
and P. jiroveciirefers to the distinct species that infects humans. The abbreviation PCP is still used to
designate Pneumocystis pneumonia. Initial infection with P. jiroveciiusually occurs in early childhood;
two-thirds of healthy children have antibodies to P. jiroveciiby ages 2 to 4 years.1 Rodent studies and
case clusters in immunosuppressed patients suggest that Pneumocystis spreads by the airborne route.
Disease probably occurs by new acquisition of infection and by reactivation of latent infection.2-11
Before the widespread use of PCP prophylaxis and antiretroviral therapy (ART), PCP occurred in 70% to
80% of patients with AIDS;12 the course of treated PCP was associated with a 20% to 40% mortality rate
in individuals with profound immunosuppression. Approximately 90% of PCP cases occurred in patients
with CD4 T-lymphocyte (CD4 cell) counts <200 cells/mm3. Other factors associated with a higher risk of
PCP included CD4 cell percentage <14%, previous episodes of PCP, oral thrush, recurrent bacterial
pneumonia, unintentional weight loss, and higher plasma HIV RNA levels.13,14 The incidence of PCP has
declined substantially with widespread use of PCP prophylaxis and ART; recent incidence among
patients with AIDS in Western Europe and the United States is <1 case per 100 personyears.15 Most
cases occur in patients who are unaware of their HIV infection or are not receiving ongoing care for
HIV,16 and in those with advanced immunosuppression (CD4 counts <100 cells/mm3).17

Clinical Manifestations In HIV-infected patients, the most common manifestations of PCP are subacute
onset of progressive dyspnea, fever, non-productive cough, and chest discomfort that worsens within
days to weeks. The fulminant pneumonia observed in patients who are not infected with HIV is less
common.18,19 In mild cases, pulmonary examination usually is normal at rest. With exertion,
tachypnea, tachycardia, and diffuse dry (cellophane) rales may be observed.19 Oral thrush is a common
co infection. Fever is apparent in most cases and may be the predominant symptom in some patients.
Extrapulmonary disease is rare but can occur in any organ and has been associated with use of
aerosolized pentamidine prophylaxis.20 Hypoxemia, the most characteristic laboratory abnormality, can
range from mild (room air arterial oxygen [pO2] 70 mm Hg or alveolar-arterial O2 difference, [A-a] DO2
<35 mm Hg) to moderate ([A-a] DO2 35 and <45 mm Hg) to severe ([A-a] DO2 45 mm Hg). Oxygen
desaturation with exercise is often abnormal but is non-specific.21 Elevation of lactate dehydrogenase
levels to >500 mg/dL is common but non-specific.22 Chest radiograph typically demonstrates diffuse,
bilateral, symmetrical interstitial infiltrates emanating from the hila in a butterfly pattern;19 however, a
chest radiograph may be normal in patients with early disease.23 Atypical radiographic presentations
also occur, such as nodules, blebs and cysts, asymmetric disease, upper lobe localization, and
pneumothorax. Spontaneous pneumothorax in a patient with HIV infection should raise the suspicion of
PCP.24,25 Cavitation, intrathoracic adenopathy, and pleural effusion are uncommon in the absence of
other pulmonary pathogens or malignancy, and their presence may indicate an alternative diagnosis.
Approximately 13% to 18% of patients with documented PCP have another concurrent cause of
pulmonary dysfunction, such as tuberculosis (TB), Kaposi sarcoma (KS), or bacterial pneumonia.26,27
Thin-section computed tomography (CT) demonstrating patchy ground-glass attenuation28,29 increases
the likelihood that a diagnostic study, such as bronchoscopy, will demonstrate PCP in patients with mild-
tomoderate symptoms and normal chest radiograph and, therefore, may be useful as an adjunct.

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Diagnosis Because clinical presentation, blood tests, and chest radiographs are not pathognomonic for
PCP, and because the organism cannot be cultivated routinely, histopathologic or cytopathologic
demonstration of organisms in tissue, bronchoalveolar lavage (BAL) fluid, or induced sputum
samples18,26,27,30 is required for a definitive diagnosis. Spontaneously expectorated sputum has low
sensitivity and should not be submitted to the laboratory to diagnose PCP. Giemsa, Diff-Quik, and
Wright stains detect both the cystic and trophic forms but do not stain the cyst wall; Gomori
methenamine silver, Gram-Weigert, cresyl violet, and toluidine blue stain the cyst wall. Some
laboratories prefer direct immunofluorescent staining. Previous studies of stained respiratory tract
samples obtained by various methods indicate the following relative diagnostic sensitivities: induced
sputum <50% to >90% (the sensitivity depends on the pathogen load and specimen quality, while the
specificity depends on the experience of the microbiologist or pathologist), bronchoscopy with BAL 90%
to 99%, transbronchial biopsy 95% to 100%, and open lung biopsy 95% to 100%. Polymerase chain
reaction (PCR) is an emerging method for diagnosing PCP.31 The sensitivity of PCR for bronchoalveolar
lavage appears to be high; the ability of PCR to distinguish colonization from disease is less clear.31-34
1,3-D-glucan (a component of fungal cell walls) may be elevated in patients with PCP, but the assays
sensitivity and specificity for establishing a PCP diagnosis are problematic,35,36 and other fungal
diseases can produce elevation. Because certain processes produce similar clinical manifestations, a
specific diagnosis of PCP should be sought rather than relying on a presumptive diagnosis, especially in
patients with moderate-to-severe disease. Treatment can be initiated before making a definitive
diagnosis because organisms persist in clinical specimens for days or weeks after effective therapy is
initiated.

Toxoplasma gondii Encephalitis (Last updated December 10, 2015; last reviewed December 10, 2015)
Toxoplasmic encephalitis (TE) is caused by the protozoan Toxoplasma gondii. Disease appears to occur
almost exclusively because of reactivation of latent tissue cysts.1-4 Primary infection occasionally is
associated with acute cerebral or disseminated disease.

Epidemiology Seroprevalence of anti-Toxoplasmaantibody varies substantially among different

geographic locales, with a prevalence of approximately 11% in the United States, versus 50% to 80% in
certain European, Latin American, and African countries.4-6 In the era before antiretroviral therapy
(ART), the 12-month incidence of TE was approximately 33% in patients with advanced
immunosuppression who were seropositive for T. gondiiand not receiving prophylaxis with drugs against
the disease. A low incidence of toxoplasmosis is seen in patients who are seronegative for T. gondii. If
patients are truly seronegative, their toxoplasmosis presumably represents one of three possible
scenarios: 1) Primary infection, 2) Re-activation of latent disease in individuals who cannot produce
detectable antibodies, or 3) Testing with insensitive assays.7,8 Clinical disease is rare among patients
with CD4 T lymphocyte (CD4) cell counts >200 cells/L. Patients with CD4 counts <50 cells/L are at
greatest risk.1,3,8,9 Primary infection occurs after eating undercooked meat containing tissue cysts or
ingesting oocysts that have been shed in cat feces and sporulated in the environment, a process that
takes at least 24 hours. In the United States, eating raw shellfish including oysters, clams, and mussels
recently was identified as a novel risk factor for acute infection.10 Up to 50% of individuals with
documented primary infection do not have an identifiable risk factor.11 The organism is not transmitted
through person-to-person contact.

Clinical Manifestations Among patients with AIDS, the most common clinical presentation of T.
gondiiinfection is focal encephalitis with headache, confusion, or motor weakness and fever.1,3,9
Patients may also present with non-focal manifestations, including only non-specific headache and
psychiatric symptoms. Focal neurological abnormalities may be present on physical examination, and in
the absence of treatment, disease progression results in seizures, stupor, and coma. Retinochoroiditis,
pneumonia, and evidence of other multifocal organ system involvement are rare in patients with AIDS.
Computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain will typically show
multiple contrast-enhancing lesions in the grey matter of the cortex or basal ganglia, often with
associated edema.1,9,12-14 Toxoplasmosis also can manifest as a single brain lesion or diffuse
encephalitis without evidence of focal brain lesions on imaging studies.15 This latter presentation tends
to be rapidly progressive and fatal.

Diagnosis HIV-infected patients with TE are almost uniformly seropositive for anti-toxoplasma
immunoglobulin G (IgG) antibodies.1,3,9,16 The absence of IgG antibody makes a diagnosis of
toxoplasmosis unlikely but not impossible. Anti-toxoplasma immunoglobulin M (IgM) antibodies usually
are absent. Quantitative antibody titers are not useful for diagnosis. Definitive diagnosis of TE requires a
compatible clinical syndrome; identification of one or more mass lesions by CT, MRI, or other
radiographic testing; and detection of the organism in a clinical sample. On imaging studies, lesions are
usually ring-enhancing and have a predilection for the basal ganglia. MRI has sensitivity superior to that
of CT studies for radiological diagnosis of TE. Positron emission tomography13 or single-photon emission
computed tomography scanning14 may be helpful in distinguishing between TE and primary central

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nervous system (CNS) lymphoma, but no imaging technique is completely specific. For TE, detection of
the organism requires a brain biopsy, which is most commonly performed by a stereotactic CT-guided
needle biopsy. Hematoxylin and eosin stains can be used for detection of T. gondii, but sensitivity is
significantly increased if immunoperoxidase staining is used and if experienced laboratories process the
specimens.17 If safe and feasible, a lumbar puncture should be performed for T. gondiipolymerase chain
reaction (PCR), as well as for cytology, culture, cryptococcal antigen and PCR for Mycobacterium
tuberculosis, Epstein-Barr Virus (EBV) and JC Virus (JCV), either at initial presentation or subsequently,
especially in patients in whom empiric therapy fails. Detection of T. gondiiby PCR in cerebrospinal fluid
(CSF) has high specificity (96% to 100%), but low sensitivity (50%), especially once specific anti-
toxoplasma therapy has been started.18-20 The differential diagnosis of focal neurological disease in
patients with AIDS most often includes primary CNS lymphoma and progressive multifocal
leucoencephalopathy (PML). In the absence of immune reconstitution inflammatory syndrome (IRIS),
PML (but not lymphoma) can be distinguished on the basis of imaging studies. PML lesions typically
involve white matter rather than gray matter, are non-contrast enhancing, and produce no mass effect.
Less common causes of focal neurologic disease in patients with AIDS include mycobacterial infection
(especially tuberculosis [TB]); fungal infection, such as cryptococcosis; Chagas disease; and pyogenic
brain abscess, particularly in IV drug abusers. Most clinicians initially rely on an empiric diagnosis, which
can be established as an objective response, documented by clinical and radiographic improvement, to
specific anti-T. gondiitherapy in the absence of a likely alternative diagnosis. Brain biopsy is reserved for
patients who fail to respond to specific therapy, although earlier biopsy should be strongly considered if
results from imaging, serology, or PCR suggest an etiology other than toxoplasmosis. In patients with
contrast-enhancing mass lesions, detection of EBV and JCV by PCR in CSF is highly suggestive of CNS
lymphoma21,22 or PML,23 respectively.
Immune Reconstitution Inflammatory
Syndrome (IRIS)
Speaker
Synonym(s): Immune Reconstitution Syndrome, Immune Restoration Disease
In HIV infection, an exaggerated inflammatory reaction to a disease-causing microorganism that
sometimes occurs when the immune system begins to recover following treatment with antiretroviral
(ARV) drugs. Immune reconstitution inflammatory syndrome (IRIS) occurs in two forms:
"unmasking" IRIS refers to the flare-up of an underlying, previously undiagnosed infection soon after
antiretroviral therapy (ART) is started; "paradoxical" IRIS refers to the worsening of a previously
treated infection after ART is started. IRIS can be mild or life-threatening. Commonly seen in patient
with low initial CD4