Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

Charles Morrison ,Jared M Baeten,Nicola Low,Joelle Brown,Landon Myer,Cynthia Kwok,R Scott Mcclelland,Saidi Kapiga,Helen Rees,Deborah Watson-Jones,Stephanie Karpoff,Lut Van Damme,Sheena Mccormack,Angela M Crook,Nuala Mcgrath,Ariane Van Der Straten,Suzanna C Francis,Rupert Kaul,Quarraisha Abdool Karim,Renee Heffron,Pai Lien Chen ,Randy M Stalter ,Sinead Delany‐Moretlwe ,Janneke Van De Wijgert ,Barbara Friedland ,Richard Hayes

doi:10.1371/journal.pmed.1001778

Abstract

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. 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. 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.

Highlights

There is ongoing debate whether hormonal contraception (HC) increases the risk of HIV acquisition [1,2,3,4]
Neither age nor herpes simplex virus type 2 infection status modified the HC–HIV relationship. This individual participant data (IPD) meta-analysis found no evidence that combined oral contraceptive (COC) or norethisterone enanthate (NET-EN) use increases women’s risk of HIV but adds to the evidence that depot-medroxyprogesterone acetate (DMPA) may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk
In multivariable analyses using a two-stage random effects approach and controlling for a common set of covariates for each study, we found no association between COC use and HIV acquisition (Table 4; Fig. 2), DMPA was associated with an increased risk of HIV acquisition, and the association between NET-EN use and HIV acquisition became weaker

Summary

Introduction

There is ongoing debate whether hormonal contraception (HC) increases the risk of HIV acquisition [1,2,3,4]. Strong evidence for an association would have important implications for sexual and reproductive health, in areas of sub-Saharan Africa where the incidence of both HIV infection and unintended pregnancy remain high [5,6,7]. HC, DMPA, has been reported to be associated with increased risk of HIV acquisition in some, but not all, studies [1,2,3,4]. 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 (NETEN) with women not using HC.

Objectives

Methods

Results

Conclusion