BACKGROUND: Daily pre-exposure prophylaxis (PrEP) with Truvada (a combination of 
emtricitabine (FTC) and tenofovir (TFV) disoproxil fumarate (TDF)) is a novel 
HIV prevention strategy recently found to prevent HIV transmission in men who 
have sex with men and heterosexual couples. We previously showed that a 
coitally-dependent Truvada regimen protected macaques against rectal SHIV 
transmission. Here we examined FTC and tenofovir TFV exposure in vaginal tissues 
after oral dosing and assessed if peri-coital Truvada also protects macaques 
against vaginal SHIV infection.
METHODS: The pharmacokinetic profile of emtricitabine (FTC) and tenofovir (TFV) 
was evaluated at first dose. FTC and TFV levels were measured in blood plasma, 
rectal, and vaginal secretions. Intracellular concentrations of FTC-triphosphate 
(FTC-TP) and TFV-diphosphate (TFV-DP) were measured in PBMCs, rectal tissues, 
and vaginal tissues. Efficacy of Truvada in preventing vaginal SHIV infection 
was assessed using a repeat-exposure vaginal SHIV transmission model consisting 
of weekly exposures to low doses of SHIV162p3. Six pigtail macaques with normal 
menstrual cycles received Truvada 24 h before and 2 h after each weekly virus 
exposure and six received placebo. Infection was monitored by serology and PCR 
amplification of SHIV RNA and DNA.
RESULTS: As in humans, the concentration of FTC was higher than the 
concentration of TFV in vaginal secretions. Also as in humans, TFV levels in 
vaginal secretions were lower than in rectal secretions. Intracellular TFV-DP 
concentrations were also lower in vaginal tissues than in rectal tissues. 
Despite the low vaginal TFV exposure, all six treated macaques were protected 
from infection after 18 exposures or 4 full menstrual cycles. In contrast, all 6 
control animals were infected.
CONCLUSIONS: We modeled a peri-coital regimen with two doses of Truvada and 
showed that it fully protected macaques from repeated SHIV exposures. Our 
results open the possibility for simplified PrEP regimens to prevent vaginal HIV 
transmission in women.