Srinivasan Sujatha, Richardson Barbra A, Wallis Jacqueline M, Fiedler Tina L, Strenk Susan M, Hoffman Noah G, Proll Sean, Chirenje Z Mike, Livant Edward W, Fredricks David N, Hillier Sharon L, Marrazzo Jeanne M
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Department of Biostatistics.
J Infect Dis. 2024 Dec 16;230(6):1444-1455. doi: 10.1093/infdis/jiae406.
Few investigations have assessed contributions of both vaginal bacteria and proinflammatory immune mediators to human immunodeficiency virus (HIV) acquisition risk in a prospective cohort.
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.
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.
Bacterial and host biomarkers for predicting HIV acquisition risk identify women at greatest risk for HIV infection and can focus prevention efforts.
在前瞻性队列研究中，很少有调查评估阴道细菌和促炎免疫介质对人类免疫缺陷病毒（HIV）感染风险的影响。
我们对参与每日口服与阴道使用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女性进行了一项巢式病例对照研究。测量了23种细菌分类群和16种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了个体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、免疫介质组合与HIV感染风险之间的关系。
我们从150名感染HIV的女性中确定了177次HIV血清转化前访视，从436名未感染HIV的女性中确定了531次访视。在调整混杂因素后，14种细菌分类群以及6种促炎细胞因子和趋化因子分别与更高的HIV风险相关。拥有全部14种分类群的女性与拥有少于14种分类群的女性相比（调整后的优势比[aOR]，4.45[95%置信区间{CI}，2.20 - 8.98]；P <.001），或者拥有全部6种免疫介质的女性与拥有少于6种免疫介质的女性相比（aOR，1.77[95% CI，1.24 - 2.52]；P <.001），感染HIV的风险更高。因子分析表明，由14种高风险细菌分类群组成的细菌因子（aOR，1.57[95% CI，1.27 - 1.93]；P < 0.001）和干扰素γ诱导蛋白10（最高四分位数：aOR，3.19[95% CI，1.32 - 7.72]；P = 0.002）导致了最高的HIV风险。
用于预测HIV感染风险的细菌和宿主生物标志物可识别出HIV感染风险最高的女性，并能集中预防工作重点。
