1. A moderately increased risk of HIV (human immunodeficiency virus) acquisition was demonstrated for all women using depot medroxyprogesterone acetate (Depo-Provera). This increase in risk was also observed for women in the general population, although to a smaller extent.
2. No evidence of increased risk of contracting HIV was demonstrated for use of oral contraceptives or for norethisterone enanthate.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Areas of the world in which high fertility rates predominate are often paralleled by high rates of HIV, and an increased risk between hormonal contraceptives and HIV risk holds vital policy implications. This meta-analysis examined observational evidence published between December 2011 and May 2014 that scrutinized the link between hormonal contraception and HIV risk. 10 of the 12 studies meeting inclusion criteria demonstrated increased risk of contracting HIV in women using depot medroxyprogesterone acetate. This risk was lower in studies primarily including women in the general population who were not in a high-risk group. No evidence of increased risk of HIV was found in the 10 studies of oral contraceptive pills or in the 5 studies of norethisterone enanthate. Overall, a moderately increased risk of contracting HIV was found for all women using depot medroxyprogesterone acetate. This study has important health policy implications for future decisions regarding the use of depot medroxyprogesterone acetate as a contraceptive, especially in areas with high rates of HIV. This meta-analysis is strong due to its strict set of inclusion criteria for studies assessed, however this led to inclusion of fewer studies, reducing the power of secondary analyses. Additionally, the two studies involving high-risk women had substantial statistical heterogeneity, moderately limiting power.
In-Depth [meta-analysis]: This meta-analysis assessed the links between various types of hormonal contraception and HIV risks. To be included in the analysis, studies had to meet specific inclusion criteria of assessing hormonal contraceptive use as an exposure, and including at least one of the following: depot medroxyprogesterone acetate, combined oral contraceptives, norethisterone enanthate, or progestin-only pills. The included studies also had to use a prospective design that excluded HIV-positive women at baseline. Studies had to include an analytic approach to minimize confounding and had to be published in a peer-reviewed journal by May 2014 with data collected in a low or middle income country.
12 of the 26 identified studies met inclusion criteria. Evidence of increased HIV risk was demonstrated in 10 studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.16–1.69). An influence analysis showed that no single study altered the results.
8 studies involving women in the general population also showed an increased risk (pooled HR 1.31, 95% CI 1.10–1.57), although to a lesser extent. For women at higher risks of contracting HIV, the estimated hazard ratios were higher – 1.73 (95% CI 1.28-2.34) for commercial sex workers and 3.93 (95% CI 1.37-11.2) for serodiscordant partnerships.
In the 10 studies of oral contraceptive pills, there was no evidence for increased HIV risk (pooled HR 1.00, 95% CI 0.86–1.16). 5 studies involving norethisterone enanthate also showed no increased risk of contracting HIV (pooled HR 1.10, 0.88–1.37).
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