Patel Eshan U, Kirkpatrick Allison R, Grabowski Mary Kate, Kigozi Godfrey, Gray Ronald H, Prodger Jessica L, Redd Andrew D, Nalugoda Fred, Serwadda David, Wawer Maria J, Quinn Thomas C, Tobian Aaron A R
Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Baltimore, Maryland, USA.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Clin Infect Dis. 2017 Mar 15;64(6):776-784. doi: 10.1093/cid/ciw847.
Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission.
A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL > 400 copies/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL > 40 copies/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL.
Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1β (adjPRR = 2.14; 95% confidence interval (CI) = 1.02-4.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28-3.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15-5.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67-3.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15-3.03) were associated with penile HIV shedding at the subsequent visit. Men with 2-4 (adjPRR = 2.36; 95% CI = 1.08-5.14) and 5-7 (adjPRR = 3.00; 95% CI = 1.28-7.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with ≤ 1 detectable cytokine. The total number of detectable cytokines was also associated with a higher penile log10 HIV VL at the subsequent visit among HIV shedders.
Pro-inflammatory cytokine production had a dose-dependent and temporal association with penile HIV shedding, suggesting that genital immune activation may increase the risk of sexual HIV transmission by driving local HIV replication.
生殖器免疫激活被怀疑可调节局部人类免疫缺陷病毒（HIV）RNA水平以及性传播HIV的风险。
在乌干达拉克伊对221名接受男性包皮环切术（MC）的HIV感染男性进行了一项前瞻性观察队列研究。在基线时以及MC术后每周一次共4次随访时，从冠状沟采集阴茎灌洗样本，检测促炎细胞因子和HIV RNA。主要分析限于175名血浆HIV病毒载量可检测到的男性（病毒载量>400拷贝/mL；共808次随访）。感兴趣的主要暴露因素是上一次术后随访时个体细胞因子和总细胞因子的检测情况。通过带有广义估计方程和稳健方差估计量的泊松回归模型估计可检测到HIV脱落（病毒载量>40拷贝/mL）的调整后患病率风险比（adjPRR），并对血浆HIV病毒载量进行调整。
在血浆病毒载量可检测到的男性中，136次随访（16.8%）检测到阴茎有HIV脱落。可检测到的白细胞介素（IL）-1β（adjPRR = 2.14；95%置信区间（CI）= 1.02 - 4.48）、IL-6（adjPRR = 2.24；95% CI = 1.28 - 3.90）、IL-8（adjPRR = 2.42；95% CI = 1.15 - 5.08）、IL-10（adjPRR = 2.51；95% CI = 1.67 - 3.80）和IL-13（adjPRR = 1.87；95% CI = 1.15 - 3.03）与随后随访时阴茎HIV脱落相关。与可检测到的细胞因子≤1种的男性相比，可检测到2 - 4种（adjPRR = 2.36；95% CI = 1.08 - 5.14）和5 - 7种（adjPRR = 3.00；95% CI = 1.28 - 7.01）细胞因子的男性在随后随访时阴茎可检测到HIV脱落的可能性更大。在HIV脱落者中，可检测到的细胞因子总数也与随后随访时阴茎HIV病毒载量的log10值较高相关。
促炎细胞因子的产生与阴茎HIV脱落存在剂量依赖性和时间相关性，这表明生殖器免疫激活可能通过驱动局部HIV复制增加性传播HIV的风险。
