Excluding HIV infection can be difficult in participants of vaccine studies due to vaccine-induced seropositivity (VISP/R), which generates positive serologic results in individuals without HIV infection. Distinguishing vaccine-induced antibodies from those due to natural infection is limited. Molecular assays (NAATs) are more accurate but have limited availability and may yield false positives. We report a case in which unexpected laboratory results complicated the initial clinical management of a former participant in an HIV vaccine clinical trial. A retrospective chart review was performed for a VISP/R participant using daily TDF/FTC PrEP. Clinical and laboratory data (immunologic and molecular tests) were analyzed. A 26-year-old cisgender homosexual man, of mixed race, participated in a clinical trial receiving four doses of an HIV vaccine, with the last dose in May 2022. He began daily TDF/FTC PrEP in January 2023, and during a follow-up visit in March (beyond the ideal interval), had detectable viral load (HIV RNA PCR: 25 copies/mL). He reported 12 partners, unprotected sex, and irregular PrEP use. On 03/28/2023, HIV antigen/antibody testing was indeterminate (reactive immunoassay, non-reactive immunoblot), and HIV RNA PCR was undetectable; PrEP was suspended during diagnostic investigation. Repeat testing on 04/12/2025 showed HIV RNA PCR undetectable, but HIV antigen/antibody testing reactive (immunoassay reactive; immunoblot reactive for gp120, gp41, and p24). Peripheral blood mononuclear cell testing for proviral HIV DNA was performed in a virology laboratory, totaling 15 attempts with different methods, all negative. In the absence of laboratory confirmation and with persistently undetectable HIV RNA, HIV infection was excluded. The patient resumed oral PrEP, with subsequent HIV RNA PCRs remaining undetectable. Diagnosing HIV infection in individuals with VISP is a clinical challenge. In this scenario, isolated positive HIV RNA PCR results must be interpreted cautiously due to potential cross-contamination and confirmatory test limitations. It is crucial to develop simple, accessible tests capable of differentiating vaccine-induced from infection-induced antibodies. Fifth-generation rapid tests detecting p24 antigen may represent a useful option.
Iglessias et al. (Sun,) studied this question.