Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition

BACKGROUND: Adolescent girls and young women aged 15‒24 years in sub-Saharan Africa are at disproportionate risk of human immunodeficiency virus (HIV) infection. Given the known association between vaginal microbial dysbiosis and HIV susceptibility, we performed an age-stratified analysis of the vaginal microbiome in South African women and compared this to their risk of HIV acquisition. METHODS: Vaginal microbiome data were generated by mass spectrometry–based proteomic analysis of cervicovaginal lavages collected from participants (n = 688) in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial. Participants were grouped by age (18–19 years, n = 93; 20–24 years, n = 326; 25–41 years, n = 269). RESULTS: Four microbiome types were identified based on predominant taxa, including Lactobacillus crispatus (CST-LC, 12.2%), Lactobacillus iners (CST-LI, 43.6%), Gardnerella vaginalis (CST-GV, 26.6%), or polymicrobial (CST-PM, 15.1%). Women aged 18–19 and 20–24 years had increased CST-PM and a non-Lactobacillus-dominant microbiome compared to those 25–41 years (odds ratio [OR], 3.14 [95% confidence interval {CI}, 1.12–7.87], P = .017; OR, 2.81 [95% CI, 1.07–7.09], P = .038, respectively; and OR, 1.65 [95% CI, 1.02–2.65], P = .028; OR, 1.40 [95% CI, 1.01–1.95], P = .030, respectively). The HIV incidence rate of women with CST-PM microbiome was 7.19-fold higher compared to women with CST-LC (hazard ratio [HR], 7.19 [95% CI, 2.11–24.5], P = .00162), which was also consistent in women aged 20–24 years (HR, 4.90 [95% CI, 1.10–21.9], P = .0375). CONCLUSIONS: Younger women were more likely to have a higher-risk polymicrobial microbiome suggesting that vaginal microbiota are contributing to increased HIV-1 susceptibility in this group. CLINICAL TRIALS REGISTRATION: NCT00441298.