Grant: Project Grant

HIV acquisition occurs during a window of 48-72 hr after sex, and is more likely in the presence of genital inflammation. We have recently shown that penile-vaginal sex causes both penile and vaginal inflammation during this same 48-72 window of HIV transmission, potentially due to the transfer of normal genital bacteria (the genital "microbiome") from one partner to another. In addition, we showed that clinical interventions targeting the "non optimal" bacteria within the genital microbiome can reduce HIV susceptibility in both the vagina and the penile foreskin. Therefore, we think that HIV transmission may be enhanced by the transfer of inflammatory genital bacteria during sex. In addition, we think that treatments targeting these bacteria BEFORE sex might reduce the probably of HIV transmission. Working with a mix of established and new colleagues, and with dedicated participants from Uganda, we aim to demonstrate that: 1) Inflammation in penis tissues, and the types of bacteria on and in the penis, are shaped in both the short and long term by the transfer of bacteria from the vagina during penile-vaginal sex. 2) That clinical treatments targeting these bacteria can reduce inflammation after sex, reducing HIV susceptibility in both the penis and vagina. These hypotheses will be tested by a well-established Canada-Uganda research collaboration, in three really unique participant cohorts. This includes a couples' study that is examining the impact of penile-vaginal sex on the genital microbiome and immune milieu in 160 Uganda couples; a cohort study examining the impact of sexual debut on penile immunology and microbiota in 200 adolescent Ugandan males; and a clinical trial of antibiotics to reduce HIV penile HIV susceptibility in 125 Ugandan men. We will also study how bacteria grown from participant swabs interact with other in the lab, and can adapt to cause inflammation in different genital tissues.