What laboratory tests are recommended for an individual seeking an HIV assessment?

HIV Assessment Laboratory Testing

For an individual seeking HIV assessment, begin with a fourth-generation HIV antigen/antibody combination assay, followed by HIV-1/HIV-2 antibody differentiation testing if reactive, and nucleic acid amplification testing (NAAT) if needed to resolve discordant results. 1, 2

Initial Screening Test

• The fourth-generation antigen/antibody combination assay is the recommended first-line screening test, detecting both HIV p24 antigen and HIV antibodies with sensitivity and specificity greater than 99.5%. 1
• This test allows detection of acute infection approximately 2 weeks earlier than antibody-only tests, reducing the window period by approximately 4 days. 1, 2
• Informed consent must be obtained before performing HIV testing (some states require written consent). 3, 4

Confirmatory Testing Algorithm

If the initial screening test is reactive:

• Perform an HIV-1/HIV-2 antibody differentiation immunoassay to distinguish between HIV-1 and HIV-2 infections. 1, 2
• If the differentiation assay is positive, HIV infection is confirmed. 4
• If the differentiation assay is negative or indeterminate, perform a qualitative or quantitative NAAT (HIV RNA test) to rule out acute HIV-1 infection. 1, 2

Never disclose a positive HIV diagnosis based on screening test alone without confirmatory testing, as false positives can occur with devastating psychological and social consequences. 2, 4

Comprehensive Baseline Testing After Confirmed Diagnosis

Once HIV infection is confirmed, the following comprehensive baseline laboratory panel should be obtained before initiating antiretroviral therapy: 3, 2

HIV-Specific Disease Monitoring Tests:

• CD4 cell count with percentage (obtain upon initiation of care, ideally 2 baseline measurements). 3
• Plasma HIV RNA viral load (using the same assay type throughout care when possible). 3
• Genotypic resistance testing (to assess for transmitted drug resistance). 3, 2
• HLA-B*5701 testing (required prior to prescribing abacavir). 3, 2
• Coreceptor tropism assay (recommended prior to prescribing CCR5 entry inhibitors). 3, 2

Safety and Baseline Laboratory Tests:

• Complete blood count with differential. 3
• Comprehensive metabolic panel (electrolytes, blood urea nitrogen, creatinine, glucose, liver enzymes including ALT, AST, bilirubin, alkaline phosphatase, albumin). 3
• Fasting lipid profile. 3
• Fasting blood glucose. 3
• Urinalysis (RBC, WBC, proteinuria, sediment). 3
• Glucose-6-phosphate dehydrogenase (screen for deficiency in appropriate racial or ethnic groups). 3

Coinfection and Comorbidity Screening:

• Hepatitis panel: Hepatitis B surface antigen, antibody to hepatitis B surface antigen or core antigen, antibody to hepatitis C virus, total hepatitis A antibody. 3, 2
• Tuberculosis screening (tuberculin skin test or interferon-gamma release assay). 3, 2
• Syphilis screening (RPR or VDRL with confirmatory treponemal testing if reactive). 3, 2
• Toxoplasma gondii serology. 3
• CMV serology (for patients at low risk for CMV infection). 3
• Varicella zoster virus serology (for those who deny history of chickenpox or shingles). 3
• HSV-2 screening (recommended by some experts). 3
• Screening for other sexually transmitted infections. 3, 2
• Cervical Pap test (consider anal Pap if indicated). 3
• Chest radiography (for patients with positive tuberculosis test result or underlying lung disease). 3

Additional Testing in Specific Populations:

• Serum testosterone level (in males with fatigue, weight loss, loss of libido, erectile dysfunction, depression, or reduced bone mineral density). 3

Special Testing Considerations

Recent High-Risk Exposure (Within 72 Hours):

• Perform both a laboratory-based antigen/antibody test AND an HIV NAAT immediately if evaluating for post-exposure prophylaxis. 1, 2
• Avoid oral fluid-based rapid HIV tests in this context, as they are less sensitive for acute infection than blood-based tests. 2

HIV-2 Testing Indications:

• Consider HIV-2 testing for persons from West Africa or other HIV-2 endemic regions (Angola, France, Mozambique, Portugal), their sexual partners, or when clinical evidence suggests HIV disease but HIV-1 tests are negative. 3, 2, 4

Infants Born to HIV-Positive Mothers:

• Do not use standard antibody testing for infants <15-18 months, as maternal antibodies cross the placenta causing false-positive results. 3, 1, 2
• Definitive diagnosis requires two positive HIV RNA PCR or viral culture tests on separate specimens. 2, 4

Critical Pitfalls to Avoid

• Window period false negatives: Antibody tests cannot rule out infection that occurred less than 6 months before testing, as HIV antibody is detectable in ≥95% of patients within 6 months of infection. 3, 4
• CD4 count variability: Be aware of substantial variation in CD4 cell counts, especially during acute illness; some experts recommend obtaining 2 baseline measurements before treatment decisions. 3
• Viral load fluctuations: HIV load may be transiently increased by vaccinations and intercurrent illnesses. 3
• Assay consistency: Monitor patients using the same HIV load assay throughout their care when possible, and be aware of changes in assay type and associated variability. 3