False-Positive Fourth-Generation HIV Screening with Low-Level Viremia in Pregnancy: A Diagnostic Challenge

Background Human immunodeficiency virus (HIV) screening is routinely performed during pregnancy to reduce the risk of perinatal transmission. Although fourth-generation HIV antigen/antibody assays have excellent sensitivity and specificity, false-positive results can occur and create significant diagnostic and management challenges. Case A gravida 3 para 2 woman in her 30s screened positive on a fourth-generation HIV assay at her initial prenatal visit. Subsequent HIV-1/2 antibody differentiation testing was negative, and HIV-1 RNA testing was undetectable. During routine third-trimester rescreening, the fourth-generation assay was again reactive, and HIV-1 RNA testing demonstrated a low-level detectable viral load of 247 copies/mL. Given concern for acute HIV infection and risk of vertical transmission, antiretroviral therapy was initiated. Extensive repeat evaluation, including repeat fourth-generation testing, qualitative and quantitative HIV-1 RNA assays, HIV genotyping, lymphocyte subset analysis, and HIV DNA polymerase chain reaction testing failed to demonstrate evidence of HIV infection. The findings were considered consistent with a false-positive HIV screening and an erroneous low-level viremia result. Conclusion Discordant HIV testing in pregnancy can present significant diagnostic uncertainty. This case highlights the importance of careful interpretation of HIV testing algorithms, multidisciplinary collaboration, and patient-centered counseling to balance prevention of perinatal transmission with avoidance of unnecessary interventions.