A Pharmacokinetic/Pharmacodynamic Model to Predict Effective HIV Prophylaxis Dosing Strategies for People Who Inject Drugs.

The Journal of Pharmacology and Experimental Therapeutics
Katy L GarrettJulie B Dumond

Abstract

The goal of this work was to evaluate dosing strategies for tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) with injection drug use with a pharmacokinetic/pharmacodynamics analysis of concentration data generated from two single-dose clinical studies conducted in healthy women. Population pharmacokinetic models were developed using measured intracellular metabolite, endogenous nucleotide competitors, and extracellular parent drug concentrations. Intracellular metabolite concentrations were normalized to endogenous competitors and compared with an EC90 target for PrEP efficacy. Monte Carlo simulations were used to select effective dose strategies of single agents (TAF, TDF, and FTC) and combinations (TDF + FTC and TAF + FTC). Daily, intermittent, and event-driven dosing regimens at varying dosage amounts were explored. When combined, TDF + FTC and TAF + FTC both provided quick (0.5 hours) and durable (up to 84 and 108 hours, respectively) protection of ≥99% after a single dose. When dosed twice per week, protection remained at 100%. Single-agent regimens provided lower estimates of protection than either combination tested. Here, the application of pha...Continue Reading

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Citations

Feb 23, 2020·Frontiers in Pharmacology·Thomas StraubingerRobert Bies
Feb 12, 2021·Infectious Diseases and Therapy·Sheldon D Fields, Elyse Tung

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