Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

Journal of Virology
Charles DobardWalid Heneine

Abstract

A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exh...Continue Reading

References

Oct 1, 1994·Physiology & Behavior·W SaltzmanD H Abbott
Jun 1, 1994·American Journal of Public Health·M Potts
Apr 1, 1996·Journal of Medical Primatology·M S SalvatoC D Pauza
Dec 15, 1996·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·I M LonginiM E Halloran
Jun 28, 2000·Journal of Medical Primatology·A B LichtenwalnerS L Hillier
May 4, 2004·The Journal of Infectious Diseases·Christopher D PilcherUNKNOWN Duke-UNC-Emory Acute HIV Consortium
Jan 20, 2005·JAMA : the Journal of the American Medical Association·Rebecca Voelker
May 27, 2005·PLoS Medicine·Jonathan WeberUNKNOWN Microbicides Development Programme
Sep 23, 2006·AIDS Research and Human Retroviruses·Jeffrey A JohnsonWalid Heneine
Sep 26, 2007·Annual Review of Medicine·Per Johan KlasseJohn P Moore
Dec 18, 2007·Cell·Jan MünchFrank Kirchhoff
May 12, 2009·Reproductive Toxicology·Ondine S von EhrensteinErin P Hines
Apr 8, 2010·Science Translational Medicine·J Gerardo García-LermaWalid Heneine
May 7, 2011·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sundaram A VishwanathanEllen N Kersh

❮ Previous
Next ❯

Citations

Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·James M SmithPatrick F Kiser
Apr 26, 2013·AIDS Research and Human Retroviruses·Joseph RomanoUNKNOWN Antiretroviral Pharmacology In HIV Prevention Think Tank Participants
Sep 8, 2012·Science Translational Medicine·Rachel SingerThomas M Zydowsky
Sep 12, 2012·Antimicrobial Agents and Chemotherapy·John A MossMarc M Baum
Nov 10, 2013·PloS One·Nabanita BiswasCharles R Wira
Jan 11, 2014·Clinical Investigation·Melanie R NicolAngela Dm Kashuba
Jan 23, 2014·Pharmaceutical Research·José das NevesBruno Sarmento
May 28, 2014·The Journal of Antimicrobial Chemotherapy·Peter L AndersonJ Gerardo García-Lerma
Mar 5, 2013·Current Opinion in HIV and AIDS·Theodore J CoryCourtney V Fletcher
Mar 8, 2012·Expert Opinion on Investigational Drugs·Tanuja N GengiahSalim S Abdool Karim
Feb 2, 2016·Advanced Drug Delivery Reviews·R Karl MalcolmDiarmaid J Murphy
Sep 18, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Justin T ClarkPatrick F Kiser
Apr 11, 2014·American Journal of Reproductive Immunology : AJRI·Janet M McNichollEllen N Kersh
Apr 12, 2014·American Journal of Primatology·Kimberley A PhillipsMary Lou Voytko
Mar 26, 2014·Journal of Clinical Pharmacology·Mackenzie L Cottrell, Angela D M Kashuba
May 3, 2015·Advanced Drug Delivery Reviews·David F KatzYajing Gao
Dec 30, 2014·Advanced Drug Delivery Reviews·José A Fernández-RomeroMelissa Robbiani
Jun 14, 2015·Virology Journal·Tara R HenningEllen N Kersh
Mar 14, 2014·Science Translational Medicine·Charles DobardWalid Heneine
May 23, 2017·Lab Animal·Koen K A Van Rompay
Nov 8, 2014·Journal of Medical Primatology·Lara E PereiraJames M Smith
Feb 10, 2018·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Andrea Ries ThurmanGustavo F Doncel
Jun 15, 2018·Journal of Clinical Pharmacology·Melanie R NicolMackenzie L Cottrell
Aug 9, 2017·Antimicrobial Agents and Chemotherapy·John W McBrideR Karl Malcolm
Feb 26, 2014·Antimicrobial Agents and Chemotherapy·Lara E PereiraJames M Smith
Apr 6, 2016·Antimicrobial Agents and Chemotherapy·Christopher J DestacheQingsheng Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.