HIV pre-exposure prophylaxis: mucosal tissue drug distribution of RT inhibitor Tenofovir and entry inhibitor Maraviroc in a humanized mouse model.

Abstract:

:Pre-exposure prophylaxis (PrEP) strategies utilizing anti-retroviral drugs show considerable promise for HIV prevention. However there is insufficient pharmacokinetic (PK) data on drug concentrations required for protection at the relevant mucosal tissues where the infection is initiated. Here we evaluated the utility of a humanized mouse model to derive PK data on two leading drugs, the RT inhibitor Tenofovir (TFV) and CCR5 inhibitor Maraviroc (MVC). Following oral dosing, both the drugs and the intracellular active TFV-diphosphate could be detected in vaginal, rectal and intestinal tissues. The drug exposures (AUC₂₄ h) were found to be higher in vaginal tissue compared to plasma with even higher levels detected in rectal and intestinal tissues. The overall trends of drug concentrations seen in humanized mice reflect those seen in the human thus establishing the utility of this model complementing the present non-human primate (NHP) models for future pre-clinical evaluations of promising HIV PrEP drug candidates.

journal_name

Virology

journal_title

Virology

authors

Veselinovic M,Yang KH,LeCureux J,Sykes C,Remling-Mulder L,Kashuba ADM,Akkina R

doi

10.1016/j.virol.2014.07.008

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

253-263

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00314-6

journal_volume

464-465

pub_type

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