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Limited studies and differential risk behaviors among men who have sex with men (MSM) in Africa calls for population-specific studies. We present results from the largest integrated biobehavioral survey among MSM in Africa to inform programming.This was a cross-sectional study using respondent-driven sampling to recruit MSM aged 18 and above. Data on sociodemographic characteristics and HIV-related risks were collected and all participants were tested for HIV, herpes simplex virus type-2 (HSV-2), hepatitis-B virus (HBV), and syphilisA total of 753 MSM with a mean age of 26.5 years participated in the study and 646 (85.7%) provided blood for biological testing. The prevalence of HIV was 22.3%, HSV-2 40.9%, syphilis 1.1%, and HBV 3.25%. Significant risk factors for HIV were age above 25, having no children [adjusted odds ratio (aOR), 2.4, 95% confidence interval (CI): 1.4 to 4.2], low HIV-risk perception (aOR, 2.6, 95% CI: 1.2 to 5.3), receptive position (aOR, 8.7, 95% CI: 1.2 to 5.3), and not using water-based lubricants (aOR, 2.6, 95% CI: 1.0 to 4.5) during the last anal sex. Also associated with HIV infection was, having sexual relationships with women (aOR, 8.0, 95% CI: 4.1 to 15.6), engaging in group sex (aOR, 3.8, 95% CI: 1.6 to 8.4), HSV-2 seropositivity (aOR, 4.1, 95% CI: 2.6 to 6.5), and history of genital ulcers (aOR, 4.1, 95% CI: 1.1 to 7.2).HIV infection and HSV-2 were highly prevalent among MSM. Low perceived HIV risk, practice of risk behaviors, and infection with HSV-2 were significant predictors of HIV infection. Behavioral interventions, HSV-2 suppressive therapies, and pre-exposure prophylaxis are highly needed.