HIV shedding from male circumcision wounds in HIV-infected men: a prospective cohort study.
BACKGROUND
A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC.


RESULTS
HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment.


CONCLUSIONS
Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Rakai Health Sciences Program, Entebbe, Uganda.
Aaron A R
AA
Tobian
Rakai Health Sciences Program, Entebbe, Uganda.
Godfrey
G
Kigozi
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Jordyn
J
Manucci
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Mary K
MK
Grabowski
Rakai Health Sciences Program, Entebbe, Uganda; Institute of Public Health, Makerere University, Kampala, Uganda.
David
D
Serwadda
Rakai Health Sciences Program, Entebbe, Uganda.
Richard
R
Musoke
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Andrew D
AD
Redd
Rakai Health Sciences Program, Entebbe, Uganda.
Fred
F
Nalugoda
Rakai Health Sciences Program, Entebbe, Uganda; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Steven J
SJ
Reynolds
Rakai Health Sciences Program, Entebbe, Uganda.
Nehemiah
N
Kighoma
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Oliver
O
Laeyendecker
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Justin
J
Lessler
Rakai Health Sciences Program, Entebbe, Uganda; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Ronald H
RH
Gray
Rakai Health Sciences Program, Entebbe, Uganda; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Thomas C
TC
Quinn
Rakai Health Sciences Program, Entebbe, Uganda; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Maria J
MJ
Wawer
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002944:Circumcision, Male; D005260:Female; D015658:HIV Infections / Q000209:etiology / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D010413:Penis / Q000601:surgery / Q000821:virology; D015995:Prevalence; D011446:Prospective Studies; D057566:Self Report; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D014946:Wound Infection / Q000150:complications / Q000821:virology*; D014947:Wounds and Injuries / Q000821:virology*
D000998:Antiviral Agents