What are the diagnosis and treatment approaches for HIV-1, HIV-2, and group O infections?

HIV-1, HIV-2, and Group O: Diagnosis and Treatment

Diagnostic Approach

For HIV-1, HIV-2, and group O infections, begin with a fourth-generation antigen/antibody combination immunoassay, followed by an HIV-1/HIV-2 antibody differentiation test if reactive, and use nucleic acid testing (NAT) for resolution of discordant results. 1, 2, 3, 4

Initial Screening

• Use a fourth-generation HIV-1/HIV-2 antigen/antibody combination assay as the primary screening test, which detects both HIV p24 antigen and antibodies to HIV-1 (including group O) and HIV-2 1, 2, 3, 4
• These assays have sensitivity and specificity greater than 99.5% and reduce the window period by approximately 4 days compared to third-generation antibody-only tests 3, 5
• Fourth-generation tests can detect infection 18-45 days post-exposure, compared to the traditional 6-month window for antibody-only tests 6, 3

Confirmatory Testing Algorithm

If the initial fourth-generation test is reactive, proceed immediately to HIV-1/HIV-2 antibody differentiation immunoassay to distinguish between HIV-1 and HIV-2 infections. 1, 2, 3, 4

• If the differentiation assay is positive for HIV-1, this confirms HIV-1 infection 2, 4
• If the differentiation assay is positive for HIV-2, this confirms HIV-2 infection 2, 4
• If the differentiation assay is negative or indeterminate despite a reactive screening test, perform HIV-1 NAT to detect acute HIV-1 infection 1, 2, 3, 4

Special Considerations for HIV-2 and Group O

HIV-2 testing should be specifically considered in persons from West Africa (endemic regions including Angola, Mozambique, Portugal, France), their sexual partners, or when clinical evidence suggests HIV disease but HIV-1 tests are negative. 1, 2

• HIV-2 prevalence in the United States is extremely low, so routine HIV-2 testing outside blood centers is not recommended unless specific risk factors are present 1
• Test for HIV-2 when HIV-1 Western blot shows an unusual indeterminate pattern (gag plus pol bands without env bands) 1
• Critical caveat: Most viral load assays have problems amplifying HIV-1 group O and do not amplify HIV-2 at all 1
• The Roche Amplicor HIV-1 Monitor version 1.0 underdetects and underestimates non-B subtypes (including group O) when quantifying viral load 1
• The Bayer HIV-1 RNA 3.0 Quantitative Assay (bDNA) likely quantifies RNA of different HIV-1 subtypes more accurately due to redundancy of multiple probes 1

Window Period and Timing Considerations

Antibody tests cannot exclude infection that occurred less than 6 months before testing, as at least 95% of infected individuals develop detectable antibodies within 6 months. 1, 2, 6

• For suspected acute infection (within first few weeks), perform NAT rather than relying solely on antibody tests, as NAT can detect HIV 10-14 days after exposure 6
• Post-exposure testing schedule: initial test at 4-6 weeks, confirmatory at 3 months (12 weeks), and final test at 6 months in rare cases of delayed seroconversion 6

Treatment Approach

All HIV-1, HIV-2, and group O infected patients should be treated with antiretroviral therapy regardless of CD4 count, using regimens appropriate for the specific virus type. 1

HIV-1 Treatment

• Recommended initial regimens for HIV-1 include dolutegravir plus 2 NRTIs, or a boosted protease inhibitor plus 2 NRTIs 1
• Genotype testing to assess transmitted NRTI and NNRTI resistance should be performed at baseline; integrase inhibitor genotyping is not routinely recommended unless exposure to a partner with InSTI resistance is suspected 1
• HLA-B*5701 testing is required before using abacavir (only needed once) 1
• CCR5 tropism testing is required when considering maraviroc 1

HIV-2 and Group O Considerations

HIV-2 is naturally resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs), requiring different treatment strategies than HIV-1. 1

• For HIV-2, avoid NNRTI-based regimens entirely 1
• Protease inhibitor-based or integrase inhibitor-based regimens are preferred for HIV-2 1
• Critical pitfall: Standard HIV-1 viral load assays do not detect HIV-2 or group O, making treatment monitoring challenging 1

Monitoring

• Once HIV RNA is below 50 copies/mL, monitor every 3 months until suppressed for at least one year, then can reduce to every 6 months if adherence is consistent 1
• Measure CD4 counts every 6 months until counts are above 250/μL for at least 1 year with viral suppression 1
• If viral load exceeds 50 copies/mL, repeat measurement within 4 weeks and reassess medication adherence and tolerability 1
• Measure viral load 4-6 weeks after starting a new antiretroviral regimen 1

Critical Pitfalls to Avoid

• Never diagnose HIV based on screening test alone—all reactive screening tests must be confirmed before diagnosis, as false positives can occur with devastating consequences 2
• Never use oral fluid-based rapid HIV tests in post-exposure prophylaxis contexts, as they are less sensitive for acute or recent infection than blood-based tests 6
• Do not rely on standard viral load assays for HIV-2 or group O monitoring, as most assays do not amplify these variants 1
• Remember that maternal antibodies persist in infants, making standard antibody testing unreliable in children under 15-18 months—use NAT or viral culture instead 2, 6
• For patients on antiretrovirals (including PrEP or PEP), both antigen/antibody test AND diagnostic NAT are required for follow-up testing due to potential viral suppression 6, 3