title: Risk of HIV-1 acquisition among women who use diff erent  types of injectable progestin contraception in South Africa:  a prospective cohort study.
abstract: BACKGROUND
  Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition.
  
  
  METHODS
  We included data from South African women who used injectable contraception while participating in theVOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679.
  
  
  RESULTS
  3141 South African women using injectable contraception were included in the present analysis: 1788 (56·9%)solely used DMPA, 1097 (34·9%) solely used NET-EN, and 256 (8·2%) used both injectable types at different times during follow-up. During 2733·7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence7·57 per 100 person-years, 95% CI 6·61–8·68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8·62 per 100 person-years, 95% CI 7·35–10·11) than among NET-EN users (5·67 per 100 person-years, 4·35–7·38;hazard ratio 1·53, 95% CI 1·12–2·08; p=0·007). This association persisted when adjusted for potential confoundingvariables (adjusted hazard ratio [aHR] 1·41, 95% CI 1·06–1·89; p=0·02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2·02 (95% CI 1·26–3·24) compared with 1·09 (0·78–1·52)for HSV-2-seronegative women (pinteraction=0·07).
  
  
  CONCLUSIONS
  Although moderate associations in observational analyses should be interpreted with caution, thesefi ndings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available.
  
  
  BACKGROUND
  National Institutes of Health, Mary Meyer Scholars Fund, and the Ruth Freeman Memorial Fund.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Noguchi
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hillier
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Balkus
authors.forename: Z Mike
authors.initials: ZM
authors.lastname: Chirenje
authors.forename: Katherine
authors.initials: K
authors.lastname: Bunge
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
authors.forename: Gonasagrie
authors.initials: G
authors.lastname: Nair
authors.forename: Thesla
authors.initials: T
authors.lastname: Palanee-Phillips
authors.forename: Pearl
authors.initials: P
authors.lastname: Selepe
authors.forename: Ariane
authors.initials: A
authors.lastname: van der Straten
authors.forename: Urvi M
authors.initials: UM
authors.lastname: Parikh
authors.forename: Kailazarid
authors.initials: K
authors.lastname: Gomez
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: Piper
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Marrazzo
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003268:Contraception Behavior / Q000706:statistics & numerical data*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D000068698:Tenofovir / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D000068698:Tenofovir; D017258:Medroxyprogesterone Acetate; C024319:norethindrone enanthate; D009640:Norethindrone