What is the recommended initial test for HIV lab diagnosis?

HIV Laboratory Diagnosis

The recommended initial test for HIV laboratory diagnosis is a fourth-generation antigen/antibody combination assay that simultaneously detects HIV p24 antigen and HIV antibodies. 1

Diagnostic Algorithm for HIV Testing

Initial Screening

• Fourth-generation HIV antigen/antibody combination assays are recommended as the initial screening tests for diagnosis of HIV infection 1
• These assays detect both HIV antibodies and p24 antigen, allowing for earlier diagnosis of infection (4-7 days after detectable virus by NAAT) 1
• Fourth-generation assays significantly reduce the diagnostic window period compared to antibody-only tests 2, 3
• The test is highly accurate with sensitivity and specificity greater than 99.5% 1

Confirmatory Testing

• Positive screening tests must be confirmed with additional testing rather than the traditional Western blot 1
• The current algorithm after a reactive fourth-generation assay includes:
  • HIV-1/HIV-2 antibody differentiation immunoassay to distinguish between HIV-1 and HIV-2 infections 1
  • If the differentiation assay is negative, nucleic acid amplification testing (NAAT) is recommended to rule out acute HIV-1 infection 1
  • If the differentiation assay is positive, viral load testing (and usually CD4 determination) is recommended to guide management 1

Benefits of Fourth-Generation Testing

• Detects HIV infection earlier than antibody-only tests, reducing the diagnostic window period 1, 3
• Can detect acute HIV infection during the highly infectious period before antibody development 4
• Helps identify HIV-2 infection, which does not respond to many first-line antiretroviral agents 4
• Studies have shown a mean reduction of the window period by approximately 4 days compared to third-generation antibody-only tests 5
• P24 antigen may be detected in serum or plasma between 14 and 22 days after infection, before antibodies become detectable 1

Special Testing Considerations

• For persons with recent high-risk exposure (within 72 hours), rapid HIV antibody testing should be performed 1
• If testing is performed in the context of post-exposure prophylaxis (PEP) evaluation, both a laboratory-based antigen/antibody test and an HIV NAT are recommended 1
• For infants born to HIV-positive mothers, definitive diagnosis should be based on laboratory evidence of HIV in blood or tissues by culture, nucleic acid, or antigen detection rather than antibody testing 1, 6
• HIV-2 testing should be considered for persons from endemic regions (parts of West Africa, Angola, Mozambique, Portugal, and France) or their sexual partners 1

Common Pitfalls and Caveats

• Antibody tests cannot rule out infection that occurred less than 6 months before the test 1, 6
• False-negative results can occur during the "window period" between infection and detectable antibodies or antigens 6
• Oral fluid-based rapid HIV tests are less sensitive for detection of acute or recent infection than blood tests and are not recommended in the context of PEP services 1
• Never disclose a positive HIV diagnosis without confirmatory testing, as false positives can occur with screening tests 6
• Rapid point-of-care tests that show reactive results require confirmation with conventional laboratory methods 1

Follow-up Testing

• For persons who have taken PEP, follow-up testing should include both a laboratory-based antigen/antibody test and a diagnostic NAT 4-6 weeks after PEP initiation 1
• High-risk individuals should be tested at least annually, while those at very high risk (MSM, injection drug users) should be tested every 3 months 1