CFAR Awards

Michael Rosenblum, PhD

Biostatistics, Johns Hopkins Bloomberg School of Public Health

Estimating the Minimum Dosing Frequency of Pre-Exposure Prophylaxis Needed to Provide a High Level of Protection Against HIV Infection

Michael Rosenblum, PhD - Image

Randomized trials of pre-exposure prophylaxis (PrEP) for preventing HIV infection have shown varying levels of effectiveness [1-7]. This raises the question of how PrEP can be tailored to different populations to achieve high levels of protection. We propose the first analyses to estimate the minimum dosing frequency needed for high level (e.g. 90%) protection against HIV for three populations: heterosexual men, heterosexual women, and injection drug users. The analyses will be based on recent advances in statistical methods for synthesizing two types of data: (i) data from pharmacokinetic-pharmacodynamic (PK/PD) studies of the relationship between PrEP pill frequency and blood concentrations of drug; and (ii) data from three recently completed randomized trials of PrEP effectiveness. Appropriately combining these data sets will allow the first characterization of the relationship between dosing frequency, blood and tissue drug concentrations, and protection against HIV infection, in the three populations listed above.
Our results will provide preliminary data for an R01 application with two primary aims. The first aim is to characterize the relationship between dosing frequency and HIV protection in a wider set of high-risk populations (including men who have sex with men) and under different modes of drug administration (including event-driven dosing, where pills are taken before and after a potential high-risk exposure). The second aim is to develop new statistical tools and software for improving future PrEP trial designs; the software will allow simulations of different trial designs tailored to specific populations and adherence patterns, and will leverage models developed in this project.