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Vaginal Bacteria and Proinflammatory Host Immune Mediators as Biomarkers of Human Immunodeficiency Virus Acquisition Risk Among African Women
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2024-08-13 , DOI: 10.1093/infdis/jiae406
Sujatha Srinivasan 1 , Barbra A Richardson 1, 2, 3 , Jacqueline M Wallis 1 , Tina L Fiedler 1 , Susan M Strenk 1 , Noah G Hoffman 4 , Sean Proll 1 , Z Mike Chirenje 5 , Edward W Livant 6 , David N Fredricks 1, 7 , Sharon L Hillier 6, 8 , Jeanne M Marrazzo 9
Affiliation  

Background Few investigations have assessed contributions of both vaginal bacteria and proinflammatory immune mediators to human immunodeficiency virus (HIV) acquisition risk in a prospective cohort. Methods We conducted a nested case-control study of African women who participated in a randomized placebo-controlled trial of daily oral versus vaginal tenofovir-based preexposure prophylaxis for HIV infection. Vaginal concentrations of 23 bacterial taxa and 16 immune mediators were measured. Relationships between individual bacterial concentrations or immune mediators and HIV risk were analyzed using generalized estimating equations in a multivariable model. Factor analysis assessed relationships between combinations of bacterial taxa, immune mediators, and HIV acquisition risk. Results We identified 177 HIV pre-seroconversion visits from 150 women who acquired HIV and 531 visits from 436 women who remained HIV uninfected. Fourteen bacterial taxa and 6 proinflammatory cytokines and chemokines were individually associated with greater HIV risk after adjusting for confounders. Women with all 14 taxa versus <14 taxa (adjusted odds ratio [aOR], 4.45 [95% confidence interval {CI}, 2.20–8.98]; P < .001) or all 6 immune mediators versus <6 mediators (aOR, 1.77 [95% CI, 1.24–2.52]; P < .001) had greater risk for HIV acquisition. Factor analysis demonstrated that a bacterial factor comprised of 14 high-risk bacterial taxa (aOR, 1.57 [95% CI, 1.27–1.93]; P < 0.001) and the interferon gamma–induced protein 10 (highest quartile: aOR, 3.19 [95% CI, 1.32–7.72]; P = 0.002) contributed to the highest HIV risk. Conclusions Bacterial and host biomarkers for predicting HIV acquisition risk identify women at greatest risk for HIV infection and can focus prevention efforts.

中文翻译:


阴道细菌和促炎宿主免疫介质是非洲女性人类免疫缺陷病毒感染风险的生物标志物



背景 很少有研究评估阴道细菌和促炎免疫介质对前瞻性队列中人类免疫缺陷病毒 (HIV) 感染风险的贡献。方法 我们对参与每日口服与阴道替诺福韦暴露前预防 HIV 感染的随机安慰剂对照试验的非洲妇女进行了一项嵌套病例对照研究。测量了 23 个细菌类群和 16 个免疫介质的阴道浓度。在多变量模型中使用广义估计方程分析单个细菌浓度或免疫介质与 HIV 风险之间的关系。因子分析评估了细菌分类群、免疫介质和 HIV 感染风险组合之间的关系。结果 我们从 150 名感染 HIV 的女性中确定了 177 次 HIV 血清转换前就诊,从 436 名未感染 HIV 的女性中确定了 531 次就诊。在调整混杂因素后,14 个细菌类群和 6 个促炎细胞因子和趋化因子与更大的 HIV 风险单独相关。所有 14 个分类群的妇女与 <14 分类群的妇女 (校正比值比 [aOR],4.45 [95% 置信区间 {CI},2.20-8.98];P < .001) 或所有 6 种免疫介质与 <6 介质 (aOR, 1.77 [95% CI, 1.24–2.52];P < .001) 感染 HIV 的风险更大。因子分析表明,细菌因子由 14 个高危细菌类群组成 (aOR, 1.57 [95% CI, 1.27–1.93];P < 0.001)和干扰素 γ 诱导的蛋白 10(最高四分位数:aOR,3.19 [95% CI,1.32–7.72];P = 0.002) 导致 HIV 风险最高。结论 用于预测 HIV 感染风险的细菌和宿主生物标志物可识别 HIV 感染风险最大的女性,并可以集中预防工作。
更新日期:2024-08-13
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