Although non-human primate studies have shown that SIV/SHIV exposure during pre-exposure prophylaxis (PrEP) with oral tenofovir can induce SIV-immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate, and found that women on PrEP had IgA with higher average HIV-1-neutralizing magnitude than women on placebo (33% versus 7%, p=0.008). Using a cut-off of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1 neutralizing IgA compared to 0% of women on placebo, p=0.09. We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (p=0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1 uninfected individuals.
Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition, and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to time-varying sexual HIV-1 exposure. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure, and further, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group as compared to placebo.