Systemic Administration of Antiretrovirals Prior to Exposure Prevents Rectal and Intravenous HIV-1 Transmission in Humanized BLT Mice

Authors

Paul W. Denton, University of Texas Southwestern Medical Center at DallasFollow
John F. Krisko, University of Texas Southwestern Medical Center at Dallas
Daniel A. Powell, University of Texas Southwestern Medical Center at Dallas
Melissa Mathias, University of Texas Southwestern Medical Center at Dallas
Youn Tae Kwak, University of Texas Southwestern Medical Center at Dallas
Francisco Martinez-Torres, University of Texas Southwestern Medical Center at Dallas
Wei Zou, University of Texas Southwestern Medical Center at Dallas
Deborah A. Payne, University of Texas Southwestern Medical Center at Dallas
Jacob D. Estes, National Cancer Institute
J. Victor Garcia, University of Texas Southwestern Medical Center at Dallas

Author ORCID Identifier

Paul W. Denton

Document Type

Article

Publication Date

1-21-2010

Publication Title

PLOS ONE

Volume

5

Issue

1

First Page

1

Last Page

11

Abstract

Successful antiretroviral pre-exposure prophylaxis (PrEP) for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT). BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003) and intravenous (Chi square = 13, df= 1, p = 0.0003) HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

Comments

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Recommended Citation

Denton PW, Krisko JF, Powell DA, Mathias M, Kwak YT, et al. (2010) Systemic Administration of Antiretrovirals Prior to Exposure Prevents Rectal and Intravenous HIV-1 Transmission in Humanized BLT Mice. PLoS ONE 5(1): e8829. doi:10.1371/journal.pone.0008829