title: Protection against rectal transmission of an emtricitabine-resistant simian/human immunodeficiency virus SHIV162p3M184V mutant by intermittent prophylaxis with Truvada.
abstract: Daily preexposure prophylaxis (PrEP) with Truvada (emtricitabine [FTC] and tenofovir disoproxil fumarate [TDF]) is a novel HIV prevention strategy recently found to reduce HIV incidence among men who have sex with men. We used a macaque model of HIV transmission to investigate if Truvada maintains prophylactic efficacy against an FTC-resistant isolate containing the M184V mutation. Five macaques received a dose of Truvada 3 days before exposing them rectally to the simian/human immunodeficiency virus mutant SHIV162p3(M184V), followed by a second dose 2 h after exposure. Five untreated animals were used as controls. Virus exposures were done weekly for up to 14 weeks. Despite the high (>100-fold) level of FTC resistance conferred by M184V, all five treated animals were protected from infection, while the five untreated macaques were infected (P = 0.0008). Our results show that Truvada maintains high prophylactic efficacy against an FTC-resistant isolate. Increased susceptibility to tenofovir due to M184V and other factors, including residual antiviral activity by FTC and/or reduced virus fitness due to M184V, may all have contributed to the observed protection.
authors.affiliation: Laboratory Branch, CDC, Division of HIV/AIDS Prevention, MS G45, 1600 Clifton Road, Atlanta, GA 30329, USA.
authors.forename: Mian-Er
authors.initials: ME
authors.lastname: Cong
authors.forename: Ae S
authors.initials: AS
authors.lastname: Youngpairoj
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Wutyi
authors.initials: W
authors.lastname: Aung
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sweeney
authors.forename: Debra L
authors.initials: DL
authors.lastname: Hanson
authors.forename: R Michael
authors.initials: RM
authors.lastname: Hendry
authors.forename: Charles
authors.initials: C
authors.lastname: Dobard
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: J Gerardo
authors.initials: JG
authors.lastname: García-Lerma
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D009154:Mutation; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004338:Drug Combinations; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D009943:Organophosphorus Compounds; D003841:Deoxycytidine; D000068679:Emtricitabine