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.