Epidemiologic studies have linked sexually transmitted infections (STIs) to an increased risk of HIV acquisition. Although the precise mechanism of this association is unclear, it is likely to be a combination of STI-induced local inflammation, disruption of mucosal surfaces, and recruitment of HIV target cells. Given that some experiments are logistically difficult or impossible to conduct in humans, nonhuman primates (NHP) as STI models of enhanced HIV susceptibility are invaluable in understanding mechanisms, magnitude of risk, and evaluating effectiveness of biomedical interventions. Advantages of using NHPs over other animal models include their relatedness to humans and availability of better immunological reagents. We have successfully developed NHP models of both vaginal and rectal STIs, and studied them in the context of simian HIV (SHIV) acquisition and coinfection, and pre-exposure prophylaxis (PrEP) efficacy. We demonstrated that vaginal Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) infections increase SHIV acquisition risk while rectal CT infections do not. Also, to study efficacy of Truvada® (the only anti-HIV medication FDA-approved for PrEP), we used a validated STI-NHP model of repeated SHIV exposures to mimic populations at high risk for HIV infection, and demonstrated that oral Truvada® maintained efficacy despite CT-TV infections, albeit with a modest loss of PrEP activity. We showed that another promising anti-HIV injectable, long-acting cabotegravir, maintained complete efficacy against vaginal SHIV acquisition in NHPs infected with CT and TV. However, these are non-ulcerative infections, which led us to develop the first NHP models for rectally and vaginally acquired syphilis, an ulcerative STI. More NHP studies are ongoing to assess risk of vaginal SHIV acquisition and PrEP efficacy in macaques coinfected with syphilis, CT, and TV. These STI-NHP models are also powerful tools to study interactions between STIs, concomitant alterations in clinical manifestations and host responses, and to evaluate specific STI-related interventions, including vaccines.

Disclosure No significant relationships.