title: Use of injectable hormonal contraception and women's risk of herpes simplex virus type 2 acquisition: a prospective study of couples in Rakai, Uganda.
abstract: BACKGROUND
  The injectable hormonal contraceptive depo-medroxyprogesterone acetate (DMPA) has been associated with increased risk of HIV acquisition, but findings are inconsistent. Whether DMPA increases the risk of other sexually transmitted viral infections is unknown. We assessed the association between DMPA use and incident herpes simplex virus type 2 (HSV2) infection in women.
  
  
  METHODS
  In this prospective study, we enrolled HIV-negative and HSV2-negative women aged 15-49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984.
  
  
  RESULTS
  Between Aug 11, 2003, and July 6, 2006, we enrolled 682 women in this study. We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using DMPA (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09-4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49-26·3; p=0·012).
  
  
  CONCLUSIONS
  Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa.
  
  
  BACKGROUND
  Bill and Melinda Gates Foundation, Doris Duke Charitable Foundation, US National Institutes of Health, and Fogarty International Center.
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grabowski
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Makumbi
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kagaayi
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Redd
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Kigozi
authors.affiliation: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Nalugoda
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Tom
authors.initials: T
authors.lastname: Lutalo
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Wawer
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda; School of Public Health, Makerere University, Kampala, Uganda.
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.affiliation: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda. Electronic address: atobian1@jhmi.edu.
authors.forename: Aaron A R
authors.initials: AAR
authors.lastname: Tobian
mesh_terms: D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006558:Herpes Genitalis / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D007267:Injections; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000069078:Seroconversion; D012747:Sexual Partners; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D017258:Medroxyprogesterone Acetate