Grant: Project Grant

Most sexual exposures to HIV do not result in virus transmission, and immune factors in the lining (mucosa) of the genital tract are key determinants of HIV susceptibility. A more activated immune environment at the site of HIV exposure (the penis, vagina or rectum) increases HIV risk, while a quiescent immune environment is protective. Our recent work has emphasized the importance of the normal penile bacteria, or the penile microbiome, in shaping HIV risk: some bacterial species cause inflammation and increase HIV risk, while others may be protective. However, the ability of antibiotics to change the penile microbiome is not known, and there is evidence that inflammatory bacteria may be transmitted to the penile microbiome during sex. Exciting preliminary work from our collaborative team shows that penile-vaginal sex and antibiotics both have major effects on penile immunology, and we think that these effects may be due to changes in the microbiome. Hypothesis. Penile microbiome components are transmitted during condomless penile-vaginal sex, and have an important impact on HIV risk that can be modified by antibiotic interventions. Three separate projects will be performed. The first will characterize the sexual transmission and stability of key bacterial components of the penile microbiome, using longitudinal samples collected before and after penile-vaginal sex in the unique SEx and Couples Study (SECS) cohort. Then we will examine how immune and bacterial factors affect the ability of clinical treatments to alter the penile microbiome, using samples from a unique randomized clinical trial performed by our team. Finally, we will characterize how key genital bacteria affect penile immunology, using in vitro tissue models.