Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya.
Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Lancet Infect Dis. 2018 May;18(5):554-564. doi: 10.1016/S1473-3099(18)30058-6. Epub 2018 Jan 26.
Disruptions of vaginal microbiota might increase women's susceptibility to HIV infection. Advances in molecular microbiology have enabled detailed examination of associations between vaginal bacteria and HIV acquisition. Therefore, this study aimed to evaluate the association between the concentrations of specific vaginal bacteria and increased risk of HIV acquisition in African women.
We did a nested case-control study of participants from eastern and southern Africa. Data from five cohorts of African women (female sex workers, pregnant and post-partum women, and women in serodiscordant relationships) were used to form a nested case-control analysis between women who acquired HIV infection versus those who remained seronegative. Deep sequence analysis of broad-range 16S rRNA gene PCR products was applied to a subset of 55 cases and 55 controls. From these data, 20 taxa were selected for bacterium-specific real-time PCR assays, which were examined in the full cohort as a four-category exposure (undetectable, first tertile, second tertile, and third tertile of concentrations). Conditional logistic regression was used to generate odds ratios (ORs) and 95% CIs. Regression models were stratified by cohort, and adjusted ORs (aORs) were generated from a multivariable model controlling for confounding variables. The Shannon Diversity Index was used to measure bacterial diversity. The primary analyses were the associations between bacterial concentrations and risk of HIV acquisition.
Between November, 2004, and August, 2014, we identified 87 women who acquired HIV infection (cases) and 262 controls who did not acquire HIV infection. Vaginal bacterial community diversity was higher in women who acquired HIV infection (median 1·3, IQR 0·4-2·3) than in seronegative controls (0·7, 0·1-1·5; p=0·03). Seven of the 20 taxa showed significant concentration-dependent associations with increased odds of HIV acquisition: Parvimonas species type 1 (first tertile aOR 1·67, 95% CI 0·61-4·57; second tertile 3·01, 1·13-7·99; third tertile 4·64, 1·73-12·46; p=0·005) and type 2 (first tertile 3·52, 1·63-7·61; second tertile 0·85, 0·36-2·02; third tertile 2·18, 1·01-4·72; p=0·004), Gemella asaccharolytica (first tertile 2·09, 1·01-4·36; second tertile 2·02, 0·98-4·17; third tertile 3·03, 1·46-6·30; p=0·010), Mycoplasma hominis (first tertile 1·46, 0·69-3·11; second tertile 1·40, 0·66-2·98; third tertile 2·76, 1·36-5·63; p=0·048), Leptotrichia/Sneathia (first tertile 2·04, 1·02-4·10; second tertile 1·45, 0·70-3·00; third tertile 2·59, 1·26-5·34; p=0·046), Eggerthella species type 1 (first tertile 1·79, 0·88-3·64; second tertile 2·62, 1·31-5·22; third tertile 1·53, 0·72-3·28; p=0·041), and vaginal Megasphaera species (first tertile 3·15, 1·45-6·81; second tertile 1·43, 0·65-3·14; third tertile 1·32, 0·57-3·05; p=0·038).
Differences in the vaginal microbial diversity and concentrations of key bacteria were associated with greater risk of HIV acquisition in women. Defining vaginal bacterial taxa associated with HIV risk could point to mechanisms that influence HIV susceptibility and provide important targets for future prevention research.
National Institute of Child Health and Human Development.
阴道微生物群的紊乱可能会增加女性感染 HIV 的易感性。分子微生物学的进步使我们能够详细研究阴道细菌与 HIV 感染获得之间的关系。因此，本研究旨在评估非洲女性阴道细菌浓度与 HIV 感染获得风险增加之间的关系。
我们对来自东非和南非的参与者进行了嵌套病例对照研究。来自五个人群队列的非洲女性（女性性工作者、孕妇和产后女性，以及处于血清不一致关系的女性）的数据用于形成 HIV 感染女性与未感染血清的女性之间的嵌套病例对照分析。广泛的 16S rRNA 基因 PCR 产物的宽范围深度序列分析应用于 55 例病例和 55 例对照的亚组。从这些数据中，选择了 20 个分类群进行细菌特异性实时 PCR 检测，这些检测在全队列中作为四个类别暴露（无法检测、第一三分位数、第二三分位数和第三三分位数的浓度）进行检查。条件逻辑回归用于生成比值比（OR）和 95%置信区间（CI）。回归模型按队列分层，并通过多变量模型生成调整后的 OR（aOR），该模型控制混杂变量。香农多样性指数用于测量细菌多样性。主要分析是细菌浓度与 HIV 感染获得风险之间的关系。
2004 年 11 月至 2014 年 8 月，我们确定了 87 名感染 HIV 的女性（病例）和 262 名未感染 HIV 的对照组女性。感染 HIV 的女性阴道细菌群落多样性较高（中位数 1·3，四分位距 0·4-2·3），而非血清阴性对照组（0·7，0·1-1·5；p=0·03）。在 20 个分类群中，有 7 个与 HIV 感染获得的几率呈浓度依赖性显著相关：Parvimonas 种 1（第一三分位数 aOR 1·67，95%CI 0·61-4·57；第二三分位数 3·01，1·13-7·99；第三三分位数 4·64，1·73-12·46；p=0·005）和种 2（第一三分位数 3·52，1·63-7·61；第二三分位数 0·85，0·36-2·02；第三三分位数 2·18，1·01-4·72；p=0·004），Gemella asaccharolytica（第一三分位数 2·09，1·01-4·36；第二三分位数 2·02，0·98-4·17；第三三分位数 3·03，1·46-6·30；p=0·010），Mycoplasma hominis（第一三分位数 1·46，0·69-3·11；第二三分位数 1·40，0·66-2·98；第三三分位数 2·76，1·36-5·63；p=0·048），Leptotrichia/Sneathia（第一三分位数 2·04，1·02-4·10；第二三分位数 1·45，0·70-3·00；第三三分位数 2·59，1·26-5·34；p=0·046），Eggerthella 种 1（第一三分位数 1·79，0·88-3·64；第二三分位数 2·62，1·31-5·22；第三三分位数 1·53，0·72-3·28；p=0·041）和阴道 Megasphaera 种（第一三分位数 3·15，1·45-6·81；第二三分位数 1·43，0·65-3·14；第三三分位数 1·32，0·57-3·05；p=0·038）。
阴道微生物多样性和关键细菌浓度的差异与女性 HIV 感染获得风险增加相关。确定与 HIV 风险相关的阴道细菌分类群可以指出影响 HIV 易感性的机制，并为未来的预防研究提供重要目标。
国家儿童健康与人类发展研究所。
