Vaccine-induced seropositivity/seroreactivity (VISP/R) on common HIV screening assays after vaccination with investigational adenovirus vector-based mosaic HIV regimens in clinical trials

Antibodies induced by prophylactic human immunodeficiency virus (HIV) vaccines can yield positive/reactive test results on commonly used HIV antibody-based, screening and confirmatory assays, referred to as vaccine-induced seropositivity/reactivity (VISP/R). Although the presence of vaccine-induced antibodies has no known direct medical consequences, VISP/R can result in misclassification of HIV infection status with potentially serious consequences. We describe the prevalence and persistence of VISP/R in adult recipients of Johnson & Johnson's investigational viral-vector mosaic HIV-1 vaccines enrolled in the APPROACH study ( NCT02315703 ) and four other clinical trials. The APPROACH study provides follow-up for up to 6.5 years post-dose-1. In participants who received the full 4-dose vaccination schedule in APPROACH and entered long-term follow-up, VISP/R persisted in 91% (50/55) at year 6.5 post-dose-1. VISP/R rates were high across all test brands employed but varied over time. In individuals whose tests became non-reactive or indeterminate at times during follow-up, no corresponding decreases were observed in HIV-1 specific antibody levels (ELISA). In the other four studies, similarly high rates of VISP/R were observed; by Week 24–26 (Month 6) post-dose-1, 80% to 100% of participants in each trial had VISP/R, and 100% had VISP/R at study end (range 2.5 to 5 years post-dose-1). Our data also demonstrated that a negative test at a single timepoint in individuals with VISP/R is not a reliable indicator of whether VISP/R has disappeared, as tests may be positive again later using the same or another brand. Our results showing the presence of VISP/R are consistent with previous reports of other investigational HIV vaccines, although prevalence and persistence varies. Importantly, HIV antibody-based tests are used to screen for HIV infection globally and guide HIV treatment in remote/resource-limited settings; therefore, affordable, simple, and rapid tests that can differentiate between vaccine-induced antibodies and infection are needed, especially once an HIV vaccine becomes available. • Rates of VISP/R are very high after investigational adenovirus vector HIV vaccines. • VISP/R persisted in 91% of vaccinees 6.5 years post dose 1 with Ad26.Mos.HIV vaccine. • VISP/R was high across multiple Ad26.Mos.HIV regimens and trials years after dose 1. • Commonly used, antibody-based HIV screening tests cannot distinguish between vaccine-induced antibodies and infection.