Microbicide-vaccine Combination Provides Significant Protection against Vaginal SHIV-162P3 Challenge in Cynomolgous Monkeys

Background: Although a number of new biomedical prevention tools have demonstrated variable success against HIV infection in clinical trials including a partially effective microbicide (tenofovir gel) and a modestly protective vaccine (the Thai RV-144 trial), their combined introduction could provide more potent protection. This study directly explores potential positive interactions.

Methods: We used a nonhuman primate model to determine whether combining a partially effective microbicide (1% tenofovir gel) with an envelope based vaccine could provide enhanced efficacy against repeat intravaginal challenge with SHIV-162P3. Vaccinated animals received three nasal priming doses containing a combination of gp140 TV1 (Clade C) and SF162 (clade B) constructs administered with R848 (TLR7/8 agonist) followed by two intramuscular boost immunizations administered with MF59.

Results: Tenofovir gel provided a 46% reduction in infection following 6 consecutive low dose intravaginal challenges (P = 0.04), where tenofovir gel in vaccinated animals provided 81% reduction (P = 0.02) and the vaccine alone failed to protect against SHIV-162P3 infection (P = 0.85). Following 12 consecutive challenges the the combination group maintained a sustained protection of 63% (P = 0.0006) while the microbicide group only provided 14% reduction in infection (P = 0.02). In a second phase, protected animals were challenged a further 12 times in the absence of microbicide. Protected animals in the vaccine group initially receiving tenofovir gel when challenged in the absence of gel maintained protection (p = 0.01) with a total risk reduction over 22 exposures of 38%, while animals initially receiving tenofovir gel were fully susceptible to infection.

Conclusions: These important findings offer the possibility that combined implementation of new biomedical prevention strategies may provide significant reduction in HIV incidence and argues for accelerated assessment of potentially beneficial combinations through randomised controlled clinical trials.