Vaginal Simian and Simian/Human Immunodeficiency Virus Prevention in Non-Human Primate Models: A Scoping Literature Review

Human immunodeficiency virus (HIV) prevention remains a significant global public health issue. In 2024, women and girls represented 44% of all new HIV infections. In Sub-Saharan Africa, they represented 62% of all new infections. Despite this burden, there is still a gap in clinical trial research on pre-exposure prophylaxis (PrEP) options for cisgender women. There are only two PrEP options approved for use in the U.S. for women: daily oral Truvada (tenofovir/emtricitabine) and Apreptude (cabotegravir). A singular prevention strategy is not feasible or desired for every single person at risk for HIV, therefore more options are needed. Non-human primate models have been an essential tool in developing and testing HIV prevention and treatment over the past 40 years. This review characterizes the evolution and current state of vaginal simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) prevention studies in non-human primate models. Out of 421 articles screened, 69 were included for this review. Main categories of research included topical microbicides, intravaginal rings, vaginal inserts, microbicide and vaccine combination methods, mucosal vaccines, and one vaginal aerosol spray. Many of the studies reported high efficacy against either single high-dose or repeated low-dose SIV/SHIV challenge(s). This review highlights some of the successes and challenges of vaginal PrEP developments and shows avenues for further research.