Individual Level Data Meta-Analysis from Pre-Exposure Prophylaxis (PrEP) Clinical Trials

  • HIV infection remains a major health problem. There is no cure for HIV infection; however, effective antiretroviral drugs can control the virus and prevent infection. Therefore, the World Health Organization recommends pre-exposure prophylaxis (PrEP) to people at risk of HIV infection. Current research findings indicate that tenofovir-based treatments are effective in lowering the probability of HIV infection in high-risk populations. However, further research is needed to firmly establish the quantitative relationship of tenofovir drug levels and the probability of HIV infection in time.
  • The goal of this project is to analyze longitudinal pharmacokinetic and HIV infection outcome data obtained from five phase-two longitudinal PrEP trials to identify sub-groups of people with higher HIV exposure risk in different target populations using placebo data (the primary methodology for this task consists of developing a time-to-infection disease model and analyzing the different covariates/characteristics that make a population higher-risk) and to identify the target concentrations of tenofovir and tenofovir diphosphate in plasma, cells, and tissue (vaginal) needed to prevent HIV infection, given treatment orally or topically by vaginal administration, through the development of PK/PD models that quantitatively relate drug concentrations to the probability of HIV infection in time.
  • The developed PK/PD framework is expected to provide key insights for interpreting study outcomes and informing future PrEP clinical trial designs and targeted interventions.