title: Association between male circumcision and incidence of syphilis in men and women: a prospective study in HIV-1 serodiscordant heterosexual African couples.
abstract: BACKGROUND
  Male circumcision is a primary HIV-1 prevention intervention for men, but whether the procedure reduces the risk of syphilis among men and their female partners is uncertain. We aimed to assess whether male circumcision was associated with incident syphilis in men and in their female partners.
  
  
  METHODS
  In this large prospective cohort study, participants were members of Kenyan and Ugandan HIV-1 serodiscordant heterosexual couples enrolled in a randomised safety and efficacy clinical trial of pre-exposure prophylaxis for HIV-1 prevention (the Partners PrEP Study). Participants attended monthly or quarterly follow-up visits for up to 36 months. Annually, syphilis serology testing was done and male circumcision status was assessed. We used multivariate Andersen-Gill survival methods, adjusted for age, sexual behaviour, and plasma HIV RNA levels of the HIV-infected partner.
  
  
  RESULTS
  4716 HIV-1 serodiscordant couples (38%) with a man with HIV were followed for a median of 2·75 years. At enrolment, 1575 (53%) men with HIV and 560 (32%) men without HIV were circumcised; an additional 69 (4%) men with HIV and 132 (5%) men without HIV were circumcised during study follow-up. 221 incident syphilis infections were reported: 46 (21%) in men with HIV (incidence 1·10 per 100 person-years), 76 (34%) in men without HIV (1·09), 54 (24%) in women with HIV (0·77), and 45 (24%) in women without HIV (1·11). Male circumcision was associated with a 42% reduction in incident syphilis in men (adjusted hazard ratio [aHR] 0·58, 95% CI 0·37-0·91) including a 62% reduction in men with HIV (0·38, 0·18-0·81), and a non-significant reduction in incident syphilis in men without HIV (0·64, 0·36-1·11). In women, circumcision of their male partners was associated with a 59% reduction in incident syphilis (aHR 0·41, 95% CI 0·25-0·69), including a 75% reduction in women without HIV (0·25, 0·08-0·76) and a 48% reduction in women with HIV (0·52, 0·27-0·97).
  
  
  CONCLUSIONS
  Male circumcision was associated with decreased risk of incident syphilis in men and women. If confirmed, these results suggest that medical male circumcision could substantially reduce incidence of syphilis and its sequelae.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Nursing, University of Washington, Seattle, WA, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Pintye
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Manhart
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Departments of Medicine and Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada; Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: Allan
authors.initials: A
authors.lastname: Ronald
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Center for Microbiology Research and Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mujugira
authors.affiliation: Center for Microbiology Research and Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; Department of Obstetrics, Gynecology and Reproductive Sciences University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Department of Reproductive Health, Moi University, Eldoret, Kenya.
authors.forename: Edwin
authors.initials: E
authors.lastname: Were
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA; Center for Microbiology Research and Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; Department of Obstetrics, Gynecology and Reproductive Sciences University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bukusi
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA. Electronic address: rheffron@uw.edu.
authors.forename: Renee
authors.initials: R
authors.lastname: Heffron
mesh_terms: D000328:Adult; D044383:Black People; D002944:Circumcision, Male / Q000706:statistics & numerical data*; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D020010:Heterosexuality; D006801:Humans; D015994:Incidence; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012737:Sex Factors; D012725:Sexual Behavior; D012747:Sexual Partners; D013587:Syphilis / Q000453:epidemiology*; D014454:Uganda / Q000453:epidemiology