HIV Disease Workup

  • Author: Nicholas John Bennett, MB, BCh, PhD; Chief Editor: Ronald A Greenfield, MD   more...
 
Updated: Nov 9, 2011
 

Approach Considerations

Screening for human immunodeficiency virus (HIV) infection is paramount, since infected individuals may remain asymptomatic for years while the infection progresses. Serologic tests are the most important studies in the evaluation for HIV infection.

Secondary testing that may be performed to assist with diagnosis or staging includes the following:

  • Viral culture
  • Lymph node biopsy
  • Proviral DNA polymerase chain reaction (PCR)
  • Genotyping of viral DNA/RNA

Staging of HIV disease is based partially on clinical presentation, but other laboratory tests can help in deciding whether to initiate or modify treatment.

Baseline laboratory studies for other infections (eg, tuberculosis) are important in the initial workup of a patient with newly diagnosed HIV infection. In addition, baseline levels of factors that may be affected by antiretroviral therapy (eg, lipids) should be measured.

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Screening for HIV Infection

The U.S. Preventive Services Task Force (USPSTF) strongly recommends that clinicians screen for HIV in all adolescents and adults at increased risk for HIV infection, and all pregnant women.[72]

The Centers for Disease Control and Prevention (CDC) recommends HIV screening for patients in all health-care settings, after the patient is notified that testing will be performed unless the patient declines (opt-out screening); the CDC recommends that persons at high risk for HIV infection be screened for HIV at least annually.[73]

Citing the benefits of early diagnosis and treatment and the failure of risk-based screening to identify a substantial proportion of HIV-infected patients early in the disease, the American College of Physicians recommends that clinicians adopt routine screening for HIV and encourage all patients to be tested.[74]

Screening assays

A high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) should be used for screening. Most ELISAs can be used to detect HIV-1 types M, N, and O and HIV-2.

A positive ELISA result should be followed with confirmatory testing in the form of one or more Western blot assays or similar specific assay. Specific diagnostic criteria vary by test. Results are typically reported as positive, negative, or indeterminate.

Testing for HIV-2 should be ensured for patients from an HIV-2 endemic area or those who have indeterminate results on HIV-1 Western blot testing. Not all HIV tests include detection of HIV-2 or Group O. In New York City, 62 cases of HIV-2 were detected over an 8-year period, of which 40 were initially misdiagnosed as HIV-1.[75]

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CD4+ T-cell Count

The CD4 T-cell count is a reliable indicator of the current risk of acquiring opportunistic infections. CD4 counts vary, and serial counts are generally a better measure of any significant changes. The reference range for CD4 counts is 500-2000 cells/μL. After seroconversion, CD4 counts tend to decrease (around 700/μL on average) and continue to decline over time. For surveillance purposes, a CD4 count under 200/μL is considered AIDS-defining in the United States owing to the increased risk of opportunistic infections at this level.

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Viral Load

Viral load in peripheral blood is used as a surrogate marker of viral replication rate. This is a surrogate because most of the viral replication occurs in the lymph nodes rather than in the peripheral blood.

The test is a quantitative amplification of the viral RNA using nucleic acid sequence-based amplification (NASBA), reverse-transcription polymerase chain reaction (RT-PCR), or similar technologies. Quantitative viral-load assays should not be used as a diagnostic tool because several false-positive misdiagnoses have been reported in the literature.

The rate of progression to AIDS and death is related to the viral load, although, on an individual level, it is poorly predictive of the absolute rate of CD4 T-cell loss. Patients with viral loads greater than 30,000/μL are 18.5 times more likely to die of AIDS than those with undetectable viral loads.

With therapy, viral loads can often be suppressed to an undetectable level (ie, < 20-75 copies/mL, depending on the assay used); this is considered optimal viral suppression. At the same time, the CD4 count rises and the risk of opportunistic infections and death is reduced. Complete inhibition of viral replication appears impossible and may be unnecessary.

Not uncommonly, successfully treated patients will demonstrate intermittent viremia, with viral loads transiently detectable at low levels (typically, < 400 copies/mL); this appears to occur more commonly with some viral load assays than others. Such “blips” are not thought to represent viral replication or to predict virologic failure.[76] Virologic failure is defined as a confirmed viral load of more than 200 copies/mL; although this is a research definition, it may be useful in clinical practice.[76]

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Secondary HIV Testing

Viral culture is expensive and time-consuming and is less sensitive in patients with low viral loads. Viral culture may be performed as part of phenotypic drug-resistance testing.

Lymph node architecture is disrupted during HIV infection. HIV DNA, RNA, and proteins may be detected with molecular techniques, and electron microscopy may reveal virions.

Proviral DNA PCR is usually performed only in newborns because conventional serologic testing is useless in these patients (maternal antibodies may persist for 9 months or longer). Two or more negative results separated by at least one month is considered a negative result.

Genotyping of viral DNA/RNA can guide therapy. Because patterns of mutations that lead to resistance to specific drugs or drug classes are now well-recognized, sequencing of the viral genome allows for the selection of specific antivirals that are more likely to elicit a response.

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Baseline Studies

Baseline studies for other infections that are important in the initial workup of a patient with newly diagnosed HIV infection include the following:

  • Purified protein derivative (PPD) skin testing for tuberculosis
  • Cytomegalovirus (CMV) testing
  • Syphilis testing
  • Rapid amplification testing for gonococcal and chlamydial infection
  • Hepatitis A, B, and C serology
  • Anti-Toxoplasma antibody
  • Ophthalmologic examination

A purified protein derivative skin test is placed to evaluate for tuberculosis infection. Chest radiography should be performed in patients with a positive PPD test result.

Serology should be performed to test for CMV infection. The presence of anti-CMV IgG indicates previous exposure to CMV. Ophthalmologic examination is used to evaluate for CMV retinitis in people with very low CD4 T-cell counts.

For syphilis screening, rapid plasma reagent (RPR) testing can be used initially, but more specific testing should be used for follow-up, as RPR can yield false-positive results. Lumbar puncture is used to evaluate neurologic symptoms.

Rapid amplification testing is used to evaluate for gonococcal infection and chlamydia in cases of sexual HIV transmission. Pelvic examination is performed in females (with wet mount for trichomoniasis).

Hepatitis A, B, and C serology is performed to determine the need for vaccination or treatment and to evaluate for chronic infection. Patients infected with hepatitis C may be candidates for treatment. Genotyping and baseline liver function tests are crucial.

Anti-Toxoplasma antibody is measured to determine whether patients have had toxoplasmosis, and thus are at risk for reactivation of infection in the event of immunocompromise. Patients with prior Toxoplasma infection require prophylaxis if their CD4+ T-cell counts drop below 100/µL.

Tests to establish baseline values of factors that may be affected by antiretroviral therapy include the following:

  • Liver function tests
  • Serum chemistries
  • Blood urea nitrogen (BUN)/serum creatinine
  • Fasting lipid panel
  • Vitamin B12 and folate levels
  • Thyroid function studies[77]

Other tests include urinalysis to evaluate for HIV-associated nephropathy and a drug screen to effectively exclude other metabolic and infectious etiologies.[78]

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Histologic Findings

Certain histologic findings are characteristic of various features of HIV infection and AIDS. The lymph node architecture is progressively disrupted; this can be reversed with effective antiviral therapy. Findings include hyperplasia, multinucleated syncytia of T cells, and loss of the normal follicular dendritic network. Nucleic acid or immunohistochemical stains for viral antigens shows virus localizing to macrophages, T cells, and dendritic cells. Electron microscopy may reveal virions or intracellular virus within phagosomes in macrophages.

Multinucleated giant cells are a characteristic finding in patients with HIV encephalopathy. Myelin pallor and microgliosis may also be observed.

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Staging

The CDC classifies HIV infection into 3 categories, according to the presence of certain infections or diseases.[53] These conditions may be exacerbated by the HIV infection or represent true opportunistic infections.

Category A is asymptomatic HIV infection without a history of symptoms or AIDS-defining conditions.

Category B is HIV infection with symptoms that are directly attributable to HIV infection (or a defect in T-cell–mediated immunity) or that are complicated by HIV infection. These include, but are not limited to, the following:

Category C is HIV infection with AIDS-defining opportunistic infections, as outlined in Pathophysiology.

These 3 categories are further subdivided based on the CD4+ T-cell count. Categories A1, B1, and C1 are characterized by CD4+ T-cell counts greater than 500/µL. Categories A2, B2, and C2 are characterized by CD4+ T-cell counts between 200/µL and 400/µL. HIV infections in patient with CD4+ T-cell counts under 200/µL are designated as A3, B3, or C3.

Importantly, once an HIV infection has been staged into a higher clinical category, it remains in that category permanently. In addition, the infection is classified based on the lowest CD4+ T-cell count in that patient.

For example, if a given HIV-positive patient recovers from a bout of Pneumocystis pneumonia (PCP) and the CD4+ T-cell count improves from 50/µL to 250/µL, that patient’s HIV infection remains classified as C3. Persons with A3, B3, and C1-3 HIV infection are considered to have AIDS. This is important to recognize, as this designation is not based solely on the previous occurrence of opportunistic infections but rather on the current risk of infection based on a reduced CD4+ T-cell count.

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Contributor Information and Disclosures
Author

Nicholas John Bennett, MB, BCh, PhD  Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University

Nicholas John Bennett, MB, BCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Shelley A Gilroy, MD  Clinical Professor of Medicine, State University of New York Upstate Medical University; Medical Director, Infection Control, University Hospital and Crouse Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Aaron Glatt, MD  Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly New Island Hospital)

Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Chief Editor

Ronald A Greenfield, MD  Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

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Electron microscopy of human immunodeficiency virus (HIV)–1 virions. Courtesy of CDC/Dr. Edwin P. Ewing, Jr.
Genome layout of human immunodeficiency virus (HIV)–1 and HIV-2.
Timeline of CD4 T-cell and viral-load changes over time in untreated human immunodeficiency virus (HIV) infection. From Wikipedia, based on an original from Pantaleo et al (1993).
Incidence of HIV infection by risk group. From the CDC Web site (copyright free) derived from the revised 2006 estimated figures.
Changes in survival of people infected with HIV. As therapies have become more aggressive, they have been more effective, although survival with HIV infection is not yet equivalent to that in uninfected people. Modified from an original published by Lohse et al (2007), "Survival of persons with and without HIV infection in Denmark, 1995-2005."
Table 1. Antiretroviral Drug Classes and Agents
Nucleoside reverse transcriptase inhibitors (NRTIs)Abacavir (Ziagen, ABC)



Didanosine (Videx, Videx EC, ddI)



Emtricitabine (Emtriva, FTC)



Lamivudine (Epivir, 3TC)



Stavudine (Zerit, Zerit XR, d4T)



Tenofovir DF (Viread, TDF)



Zalcitabine (Hivid, ddC)*



Zidovudine (Retrovir, ZDV, AZT)



Protease inhibitors (PIs)Amprenavir (Agenerase, AVP)*



Atazanavir (Reyataz , ATV)



Darunavir (Prezista, DRV)



Fosamprenavir (Lexiva, f-APV)



Indinavir (Crixivan, IDV)



Lopinavir and ritonavir (Kaletra, LPV/r)



Nelfinavir (Viracept, NFV)



Ritonavir (Norvir, RTV)



Saquinavir (Invirase [hard gel] capsule, SQV)



Tipranavir (Aptivus, TPV)



Non-nucleoside reverse transcriptase inhibitors (NNRTIs)Delavirdine (Rescriptor, DLV)



Efavirenz (Sustiva, EFV)



Etravirine (Intelence, ETR)



Nevirapine (Viramune, NVP)



Rilpivirine (Edurant)



Fusion inhibitorsEnfuvirtide (Fuzeon, T-20)
Cellular chemokine receptor (CCR5) antagonistsMaraviroc (Selzentry, MVC)
Integrase inhibitorsRaltegravir (Isentress, RAL)
*No longer available on market
Table 2. Antiretroviral Combination Products
Drug Content per Tablet/Capsule*Brand NameAdult Dose (≥40 kg)
Abacavir 600 mg



Lamivudine 300 mg



Epzicom1 tab PO qd
Abacavir 300 mg



Lamivudine 150 mg



Zidovudine 300 mg



Trizivir1 tab PO bid
Efavirenz 600 mg



Emtricitabine 200 mg



Tenofovir DF 300 mg



Atripla1 tab PO qd on empty stomach
Emtricitabine 200 mg



Rilpivirine 25 mg



Tenofovir DF 300 mg



Complera1 tab PO qd with a meal
Emtricitabine 200 mg



Tenofovir DF 300 mg



Truvada1 tab PO qd



CrCl 30-49 mL/min: 1 tab PO q48h



CrCl < 30 mL/min: Do not administer



Lamivudine 150 mg



Zidovudine 300 mg



Combivir1 tab PO bid
*Not indicated for patients requiring dosage adjustments (eg, weight < 40 kg, renal impairment, hepatic impairment, dose-limiting adverse effects) unless otherwise stated.
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