期刊
CLINICAL INFECTIOUS DISEASES
卷 64, 期 6, 页码 776-784出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciw847
关键词
human immunodeficiency virus (HIV); male circumcision; immune activation; genital inflammation; sexual transmission
资金
- Bill and Melinda Gates Foundation [22006.03]
- Doris Duke Charitable Foundation [2011036]
- Fogarty International Center [1D43TWOO9578-01]
- National Institutes of Health [K01AI125086-01, 1K23AI093152-01A1]
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Background. Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission. Methods. 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. Findings. Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1 beta (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 log 10 HIV VL at the subsequent visit among HIV shedders. Interpretation. 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.
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