Risk Factors Associated with HIV Acquisition in Males Participating in HIV Vaccine Efficacy Trials in South Africa

In South Africa, HIV acquisition risk has been studied less in people assigned male at birth. We studied the associations between risk behaviors, clinical features and HIV incidence amongst males in two South African HIV preventive vaccine efficacy trials. We used Cox proportional hazards models to test for associations between demographics, sexual behaviors, clinical variables and HIV acquisition among males followed in the HVTN 503 (n = 219) and HVTN 702 (n = 1611) trials. Most males reported no male sexual partners (99.09% in HVTN 503) or identified as heterosexual (88.08% in HVTN 702). Annual HIV incidence was 1.39% in HVTN 503 (95% CI 0.76–2.32%) and 1.33% in HVTN 702 (95% CI 0.80–2.07%). Increased HIV acquisition was significantly associated with anal sex (HR 6.32, 95% CI 3.44–11.62), transactional sex (HR 3.42, 95% CI 1.80–6.50), and non-heterosexual identity (HR 16.23, 95%CI 8.13–32.41) in univariate analyses and non-heterosexual identity (HR 14.99, 95% CI 4.99–45.04; p < 0.01) in multivariate analysis. It is appropriate that prevention efforts in South Africa, although focused on the severe epidemic in young women, also encompass key male populations, including men who have sex with men, but also men who engage in anal or transactional sex. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10461-023-04025-z.