Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical Candida colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical Candida colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry). While hormonal contraceptive type did not influence incidence of Candida colonization or hyphae, hyphae presence was associated with significantly elevated concentrations of IL-22, IL-17A and IL-17F, all produced by Th17 cells, but not of other cytokines, such as IL-1b or IL-6, after adjustment for confounders. Subclinical Candida colonization was associated with reduced frequencies of Th17-like cells and elevated frequencies of CCR6-CCR10 T cells. Women with Candida hyphae were less likely to have bacterial vaginosis (BV). Persistent, subclinical colonization with Candida over 16 weeks was associated with significant increases in Th17-related cytokine concentrations and highly activated Th17-like and CCR6-CCR10 T-cell frequencies. These data suggest that vaginal Candida colonization and hyphae increase Th17-related cytokines, but not overall female genital tract inflammation in Sub-Saharan African adolescents. Persistent Candida colonization, even when asymptomatic, may increase Th17 cell frequencies and related cytokines and thereby could subsequently increase HIV risk, although the causal relationship requires confirmation.
