The Pharmacokinetics and Viral Activity of Tenofovir in the Male Genital Tract

Abstract

OBJECTIVE: To measure tenofovir (TFV) concentrations in the male genital tract (GT) after single and multiple doses of tenofovir disoproxil fumarate (TDF) and evaluate the HIV-1 RNA response to monotherapy. DESIGN AND METHODS: A pharmacokinetic study of blood plasma (BP) and GT TFV concentrations in 9 men was conducted after 1 and > or =14 doses of TDF. TFV concentrations were measured by validated high-performance liquid chromatography-ultraviolet or tandem mass spectrometry methods, and HIV-1 RNA was measured using Roche (Roche Molecular Systems, Branchburg, NJ) or bioMerieux (bioMerieux, Durham, NC) kits. RESULTS: TFV GT concentrations were 4.4-fold +/- 5.1-fold higher than BP after dose 1 and 5.1-fold +/- 6.8-fold higher than BP after dose 14. Intracellular GT TFV-diphosphate concentrations were 9.4-fold higher than BP after dose 1 and 17.5-fold +/- 22.6-fold higher after dose 7. After 14 days ofTDF monotherapy, HIV-1 RNA decreased by 0.9 log10 copies/mL in blood and 1.0 log10 copies/mL in the GT. CONCLUSIONS: High TFV concentrations were achieved rapidly in the GT of all subjects after single and multiple doses and potently reduced BP and GT HIV-1 RNA levels.