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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study
Clinical Infectious Diseases, Volume 64, No. 6, Year 2017
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Description
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)-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. 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. © 2016 The Author. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC5850455/bin/ciw847_supplementary_data.zip
Authors & Co-Authors
Patel, Eshan U.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins University
Kirkpatrick, Allison R.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Grabowski, Mary Kate
United States, Baltimore
Johns Hopkins University
Uganda, Kalisizo
Rakai Health Sciences Program
Kigozi, Godfrey G.
Uganda, Kalisizo
Rakai Health Sciences Program
Gray, Ronald H.
United States, Baltimore
Johns Hopkins University
Uganda, Kalisizo
Rakai Health Sciences Program
Prodger, Jessica L.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins University
Redd, Andrew D.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins University
Nalugoda, Fred Kakaire
Uganda, Kalisizo
Rakai Health Sciences Program
Serwadda, David Musoke
Uganda, Kalisizo
Rakai Health Sciences Program
Uganda, Kampala
Makerere University
Quinn, Thomas C.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Baltimore
Johns Hopkins University
Uganda, Kalisizo
Rakai Health Sciences Program
Tobian, Aaron A.R.
United States, Baltimore
Johns Hopkins University
Statistics
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1093/cid/ciw847
ISSN:
10584838
Research Areas
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative
Study Locations
Uganda
Participants Gender
Male