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

Abstract 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. Young women are at disproportionate risk of HIV infection. In this study, polymicrobial vaginal microbiomes that predict increased risk of HIV acquisition are more common in younger women, which may be a contributing factor to health disparities in HIV.