Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel

The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66 in the genital tract and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (p=0.03), p24 (p=0.002) and p66 (p=0.009) in plasma and genital tract (GT) in women assigned to tenofovir than placebo gel at multiple time-points post-infection. Notably, p66 IgA titres in the GT and plasma were significantly higher in the tenofovir compared to the placebo arm (p<0.05). Plasma titres for 9 of the ten HIV-IgG specificities predicted genital tract levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel.