Efficacy of Vaginally Administered Gel Containing Emtricitabine and Tenofovir Against Repeated Rectal SHIV Exposures in Macaques

Efficacy of Vaginally Administered Gel Containing Emtricitabine and Tenofovir Against Repeated... Abstract Vaginal microbicides containing antiretrovirals (ARV) have shown to prevent vaginally acquired HIV but these products may not protect women who engage in anal sex. Intravaginal dosing with ARVs have shown to result in drug exposures in rectal tissues, thus raising the possibility of dual compartment protection. To test this concept, we investigated whether intravaginal dosing with emtricitabine (FTC)-tenofovir (TFV) gel, which fully protected macaques against repeated vaginal exposures to simian human immunodeficiency virus (SHIV), protects against rectal SHIV exposures. Pharmacokinetic (PK) studies revealed rapid distribution of FTC and TFV to rectal tissues and luminal fluids, albeit at concentrations 1-2 log10 lower than those in the vaginal compartment. Efficacy measurements against repeated rectal SHIV challenges demonstrated a 4.5-fold reduction in risk of infection in macaques that received intravaginal FTC/TFV compared to placebo gel (p=0.047; log-rank test). These data support the concept of dual compartment protection by vaginal dosing and warrants developing ARV-based vaginal products with improved bidirectional dosing. HIV PrEP, topical antiretrovirals, bi-compartmental dosing, macaque model, repeat-challenge © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Infectious Diseases Oxford University Press

Efficacy of Vaginally Administered Gel Containing Emtricitabine and Tenofovir Against Repeated Rectal SHIV Exposures in Macaques

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
ISSN
0022-1899
eISSN
1537-6613
D.O.I.
10.1093/infdis/jiy301
Publisher site
See Article on Publisher Site

Abstract

Abstract Vaginal microbicides containing antiretrovirals (ARV) have shown to prevent vaginally acquired HIV but these products may not protect women who engage in anal sex. Intravaginal dosing with ARVs have shown to result in drug exposures in rectal tissues, thus raising the possibility of dual compartment protection. To test this concept, we investigated whether intravaginal dosing with emtricitabine (FTC)-tenofovir (TFV) gel, which fully protected macaques against repeated vaginal exposures to simian human immunodeficiency virus (SHIV), protects against rectal SHIV exposures. Pharmacokinetic (PK) studies revealed rapid distribution of FTC and TFV to rectal tissues and luminal fluids, albeit at concentrations 1-2 log10 lower than those in the vaginal compartment. Efficacy measurements against repeated rectal SHIV challenges demonstrated a 4.5-fold reduction in risk of infection in macaques that received intravaginal FTC/TFV compared to placebo gel (p=0.047; log-rank test). These data support the concept of dual compartment protection by vaginal dosing and warrants developing ARV-based vaginal products with improved bidirectional dosing. HIV PrEP, topical antiretrovirals, bi-compartmental dosing, macaque model, repeat-challenge © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The Journal of Infectious DiseasesOxford University Press

Published: May 21, 2018

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