Impact of herpes simplex virus type 2 and human immunodeficiency virus dual infection on female genital tract mucosal immunity and the vaginal microbiome

Background: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. Methods: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. Results: Significant differences in the concentrations of interferon-γ(P =. 002), tumor necrosis factor-α (P =. 03), human beta defensin 1 (P =. 001), secretory leukocyte protease inhibitor (P =. 01), and lysozyme (P =. 03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P =. 0046). Specifically, when comparing HIV-1⁺/HSV-2⁺ to HIV-1^-/HSV-2^- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV⁺ versus HIV^- women (39 versus 12) (P =. 04), but there were no significant differences when comparing outbreak to non-outbreak visits. Conclusions: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.