title: Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.
abstract: BACKGROUND
  Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.
  
  
  RESULTS
  Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship.
  
  
  CONCLUSIONS
  This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
authors.affiliation: Clinical Sciences, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Morrison
authors.affiliation: Biostatistics, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Pai-Lien
authors.initials: PL
authors.lastname: Chen
authors.affiliation: Biostatistics, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kwok
authors.affiliation: Department of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Department of Epidemiology, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Joelle
authors.initials: J
authors.lastname: Brown
authors.affiliation: Medical Research Council, Comprehensive Clinical Trials Unit at UCL, University College London, London, United Kingdom.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Crook
authors.affiliation: Department of Global Health, Bill & Melinda Gates Foundation, Seattle, Washington, United States of America.
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
authors.affiliation: Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Sinead
authors.initials: S
authors.lastname: Delany-Moretlwe
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Suzanna C
authors.initials: SC
authors.lastname: Francis
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Friedland
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hayes
authors.affiliation: Department of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Renee
authors.initials: R
authors.lastname: Heffron
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Saidi
authors.initials: S
authors.lastname: Kapiga
authors.affiliation: Center for the AIDS Program of Research in South Africa, University of Kwa-Zulu Natal, Durban, South Africa.
authors.forename: Quarraisha Abdool
authors.initials: QA
authors.lastname: Karim
authors.affiliation: Diversity Research Programs, Multicenter Protocols Group, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Karpoff
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.affiliation: Department of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: R Scott
authors.initials: RS
authors.lastname: McClelland
authors.affiliation: Department of Epidemiology, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.affiliation: Department of Social Statistics and Demography, Academic Unit of Primary Care, Population Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Nuala
authors.initials: N
authors.lastname: McGrath
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Landon
authors.initials: L
authors.lastname: Myer
authors.affiliation: Wits Reproductive Health and HIV Institute, Johannesburg, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: Rees
authors.affiliation: Women's Global Health Imperative, RTI International, San Francisco, California, United States of America.
authors.forename: Ariane
authors.initials: A
authors.lastname: van der Straten
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Watson-Jones
authors.affiliation: Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Merseyside, United Kingdom.
authors.forename: Janneke H H M
authors.initials: JH
authors.lastname: van de Wijgert
authors.affiliation: Clinical Sciences, FHI 360, Durham, North Carolina, United States of America.
authors.forename: Randy
authors.initials: R
authors.lastname: Stalter
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Low
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D012307:Risk Factors
chemical_list: D003271:Contraceptive Agents, Female; D017258:Medroxyprogesterone Acetate; C024319:norethindrone enanthate; D009640:Norethindrone