An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

Chelsea B. Polis, Kathryn M. Curtis, Philip C Hannaford, Sharon J. Phillips, Tsungai Chipato, James N. Kiarie, Daniel J Westreich, Petrus S. Steyn

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)
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Objective and design: Some studies suggest that specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.

Methods: We searched for articles published between 15 January 2014 and 15 January 2016 and hand-searched reference lists. We identified longitudinal studies comparing users of a specific hormonal contraceptive method against either nonusers of hormonal contraception or users of another specific hormonal contraceptive method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus non-use of hormonal contraception.

Results: We identified 10 new reports of which five were considered ‘unlikely to inform the primary question’. We focus on the other five reports, along with nine from the previous review, which were considered ‘informative but with important limitations’. The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate, and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher quality studies on DMPA (or nondisaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher quality studies of hazard ratio 1.4.

Conclusion: Although confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely hazard ratio 1.5 or less. Data for other hormonal contraceptive methods, including norethisterone enanthate, are largely reassuring.

Original languageEnglish
Pages (from-to)2665–2683
Number of pages19
Issue number17
Early online date5 Aug 2016
Publication statusPublished - 13 Nov 2016

Bibliographical note

We are grateful to Sharon Achilles for her thoughtful input related to describing potential biological mechanisms, and to all study investigators who provided
additional information about their analyses. WHO provided support for the writing of this systmatic review and for the writing group to attend a working meeting in Geneva, Switzerland in October 2015. D.J.W. was partially funded by NIH DP2-HD-08-4070. The review was conducted independently of the WHO guidance development process; and conclusions represent the independent opinions of the authors. The findings and conclusions in this article do not necessarily reflect the positions and policies of the donor. Role of authors: The World Health Organization (J.N.K. and P.S.S.) initiated the idea to conduct this systematic review update. C.B.P. led the conduct of the systematic review, including conducting the systematic literature search and drafting the manuscript. C.B.P., K.M.C., and P.C.H. screened titles, abstracts, and full-text manuscripts to determine study inclusion. S.J.P. conducted the statistical meta-analysis. All coauthors (C.B.P., K.M.C., P.C.H., S.J.P., T.C., J.N.K., D.J.W., and P.S.S.) participated in framing the study question, developing the quality criteria, abstracting study information and assessing study quality, interpreting the data, and contributing to the writing and editing of the manuscript.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Guttmacher Institute, the Centers for Disease Control and Prevention, the World Health Organization, the National Institutes of Health, or other institutions with which the authors are affiliated.


  • contraceptive implants
  • depot medroxyprogesterone acetate
  • HIV acqisition
  • hormonal contraception
  • injectable contraception
  • norethisterone enanthate
  • oral contraception
  • systematic review


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