Maria Garcia-Cremades Mira, PhD

There are approximately 1.8 million new HIV infections occurring each year. To reduce the risk of infection, the World Health Organization recommends people at high-risk use preexposure prophylaxis (PrEP) therapy. Tenofovir has proven efficacy in lowering the probability of HIV infection in high-risk populations. However, the prophylactic concentration of tenofovir has not been reliably characterized using HIV outcome as the main endpoint and with large databases including different populations at high-risk of infection. Identifying characteristics of high-risk individuals and predictors of infection within these target populations is essential to improve PrEP access, use, and efficacy and to curb HIV transmission. This research aims first to develop an algorithm to quantitatively estimate an individual’s risk of HIV infection and second to describe the concentration-response relationships of tenofovir in plasma and effect sites (cells and tissue), adherence, and other influential variables in PrEP therapy, through the development of comprehensive pharmacokinetic-pharmacodynamic (PKPD) models. Data from 13,727 individuals obtained from large PrEP randomized controlled trials (iPrEX, VOICE, Partners, Bangkok and TDF2) with multiple HIV risk groups (men and transgender women who have sex with men, young women at high sexual risk, HIV negative partner of serodiscordant heterosexual couples, people who inject drugs, and high-risk heterosexual individuals) involving treated (oral and topical vaginal dosing) and placebo arms will be used. The resultant PKPD framework will provide a quantitative understanding of HIV risk in target populations and estimate the target in vivo drug concentration to prevent HIV infection. These models could be used to optimize prevention strategies, to guide future PrEP clinical trials, and to inform the development of new PrEP formulations.