Abstract
The genital tract of African women has been shown to differ from what is currently accepted as ‘normal’, defined by a pH≤4.5 and lactobacilli-dominated microbiota. Adolescent girls and young women (AGYW) from sub-Saharan Africa are at high risk for HIV, and we hypothesized that specific biological factors are likely to be influential. This study aimed to compare characteristics of vaginal health in HIV-negative AGYW (16-22-years-old), from two South African communities, to international norms. We measured plasma hormones, vaginal pH, presence of BV (Nugent scoring), sexually transmitted infections (multiplex PCR for Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis, Mycoplasma genitalium) and candidiasis (Gram stain) in AGYW (n = 298) from Cape Town and Soweto. Cervicovaginal microbiota was determined by 16S pyrosequencing; 44 genital cytokines were measured by Luminex; and cervical T-cell activation/proliferation (CCR5, HLA-DR, CD38, Ki67) was measured by multiparametric flow cytometry. 90/298 (30.2%) AGYW were negative for BV, candidiasis and bacterial STIs. L. crispatus and L. iners were the dominant bacteria in cervicovaginal swabs, and the median vaginal pH was 4.7. AGYW with L. crispatus-dominant microbiota (42.4%) generally had the lowest cytokine concentrations compared to women with more diverse microbiota (34/44 significantly upregulated cytokines). Frequencies of CCR5+CD4+ T-cells co-expressing CD38 and HLA-DR correlated positively with interleukin (IL)-6, TNF-α, GRO-α, macrophage inflammatory protein (MIP)-1α, and IL-9. While endogenous oestrogen had an immune-dampening effect on IL-6, TNF-related apoptosis-inducing ligand (TRAIL) and IL-16, injectable hormone contraceptives (DMPA and Net-EN) were associated with significantly lower endogenous hormone concentrations (p<0.0001 for oestrogen and progesterone) and upregulation of 34/44 cytokines. Since genital inflammation and the presence of activated CD4+ T cells in the genital tract have been implicated in increased HIV risk in South African women, the observed high levels of genital cellular activation and cytokines from AGYW may point towards biological factors increasing HIV risk in this region.
Highlights
More than seventy percent of all new HIV infections occur in sub-Saharan Africa (SSA), with young women being three times more likely to become HIV-infected than their age-matched male counterparts [1,2]
To evaluate the healthy genital environment in AGYW from Africa in the context of factors that can influence HIV risk, we focused on vaginal pH, genital cytokine concentrations, cervical cellular activation and vaginal microbiota as biomarkers for risk
In this sub-group of healthy women, we found that injectable hormone contraceptive (HC) use Defining genital health in African adolescents and microbial dysbiosis increased genital inflammation, while endogenous oestrogen concentrations had an immune-dampening effect
Summary
More than seventy percent of all new HIV infections occur in sub-Saharan Africa (SSA), with young women (aged 15–24) being three times more likely to become HIV-infected than their age-matched male counterparts [1,2]. Several socio-behavioural factors have been proposed to influence these high incidence rates of HIV in SSA, including gender inequality, limited access to sexual and reproductive health services, and age disparity between sexual partners [2]. These factors cannot fully explain the higher HIV prevalence seen in young women and it is likely that biological factors contribute to risk. We have previously shown that the genital tract chemokines interferon gamma-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and interleukin (IL)-8 were associated with >3-fold higher HIV risk in women [3]. Compared to women from the United States, African women have higher frequencies of activated cervical T-cells [6] and African American women had higher genital pH than their white American counterparts (pH 4.7 vs 4.2) [7], more diverse vaginal microbiota, and lower relative abundance of Lactobacillus spp. ( L. crispatus) [7,8,9]
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