Antiretroviral Pharmacology for PrEP (pre-exposure prophylaxis)
Angela DM Kashuba, BScPhm, PharmD, DABCP
Associate Professor of Pharmacy
Director, UNC CFAR Clinical Pharmacology and Analytical Chemistry Core
University of North Carolina at Chapel Hill
Introduction
The purpose of this presentation is to review drug exposure in the genital tract of men and women
-- generation of pharmacology data
-- extracellular GT drug concentrations in men and women
-- intracellular GT drug concentrations in men
-- predicting high concentrations in the genital tract
Review effect of antiretroviral therapy on HIV RNA in patients with established infection
-- Biology data not generated to test hypothesis that drugs differ
1. assume drugs reducing GT HIV RNA concentrate in GT fluid
2. no resistance data exist with enough power demonstrating drug concentrations matter
- High drug concentrations = potent and sustained activity
- Moderate drug concentrations = activity but resistance
--Low drug concentrations = no activity and no resistance
Genital Tract Pharmacology is looking for--
The combination (or combinations) of antiretroviral therapies that best suppress or eliminate HIV from the genital tract is (are) currently unknown.
Infectivity or risk of HIV transmission is related to the quantity of virus present in genital secretions, and it has been shown that antiretrovirals decrease HIV RNA in the GT. Therefore, a reasonable HIV prevention strategy includes the use of effective ARVs. This is the goal of both pre-exposure prophylaxis and post-exposure prophylaxis.
Yet information on optimal agents for these applications is sparse. Current guidelines for nonoccupational exposure are based on animal studies and observational data. In the case of PEP and PrEP for sexual transmission, to be most effective the optimal agents should rapidly achieve high GT concentrations.
Drugs rapidly achieving higher concentrations in the genital tract should be best suited to this purpose.
The research is designed to direct policy to assist the development of rational guidelines for use of PrEP regimens
