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Meta-Analysis Shows Injectable Hormonal Contraception Linked to HIV Infection Risk

Women who use the long-acting injectable contraceptive Depo-Provera had a modest but significant increase in the risk of contracting HIV infection, according to a meta-analysis of 12 studies published in the January 8Lancet Infectious Diseases. However, there was no increase in risk for women using birth control pills.

A number of studies over the years have looked at whether use of hormonal contraception raises the risk of HIV infection, but results have been inconsistent, with some seeing an increased risk and others seeing no difference. The reason for this association remains unclear, but contraceptive hormones may alter vaginal or cervical tissues or affect local immune response.

Lauren Ralph, Nancy Padian, and colleagues from the University of California at Berkeley School of Public Health and colleagues performed a meta-analysis of existing study data on various hormonal contraceptive methods including birth control pills and the injectables depot medroxyprogesterone (DMPA or Depo-Provera) and norethisterone enanthate (NET-EN).

Building on a previous systematic review, they searched the PubMed medical literature database for articles published between December 2011 and June 2014, as well as abstracts presented at International AIDS Society conferences and the annual Conference on Retroviruses and Opportunistic Infections (CROI). The researchers identified a total of 26 relevant studies, 12 of which met their inclusion criteria, a majority of which were conducted in sub-Saharan Africa.

Results

• The 10 studies of Depo-Provera -- which included a total of more than 39,500 women -- showed evidence of an overall increase in HIV infection risk among women using this method compared to those using other methods or no contraception (pooled hazard ratio [HR] 1.40, or a 40% increased risk).
• Looking at the 8 studies of women using Depo-Provera in the general population, the elevated risk of HIV was a bit lower (pooled HR 1.31, or a 31% increase) than it was when including 2 studies of women at high risk for infection such as sex workers and women with HIV positive partners (the variability between these 2 studies -- HR 1.73 and 3.93 -- was too great to calculate a pooled estimate).
• There was no evidence of an increased risk of HIV infection in the 10 studies of combined or progestin-only oral contraceptive pills (pooled HR 1.00).
• There was also no significant increased risk seen in the 5 studies of norethisterone enanthate (pooled HR 1.10).

"Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population," the study authors concluded. "Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive."

"The moderate elevation in risk observed in our study is not enough to justify a complete withdrawal of [Depo-Provera] for women in the general population," lead author Ralph stated in a Lancet media release. "Banning [Depo-Provera] would leave many women without immediate access to alternative, effective contraceptive options. This is likely to lead to more unintended pregnancies, and because childbirth remains life-threatening in many developing countries, could increase overall deaths among women."

In an accompanying commentary Christopher Colvin from the University of Cape Town and Abigail Harrison from Brown University School of Public Health discussed the controversy arising from prior conflicting research.

"Currently, the increasingly narrow and fierce debates over the HIV and depot medroxyprogesterone acetate link have focused on whether a large randomized controlled trial should be done to better understand this link," they wrote. "Like many scientific controversies, views have become hardened, personal, financial, or political agendas have been suggested, and there has even been intrigue in the form of leaked copies of articles under peer review. Both sides have raised important, compelling arguments, but their partisan character can weaken the quality of the debates and restrict the view of the complex relation between evidence, policy, and practice."

"The most important next steps for women all over the world are to examine ways to broaden women’s contraceptive options and increase uptake of other safe and effective contraceptive methods, and to step up research on new contraceptive methods, especially those that protect against both HIV and pregnancy," senior author Padian told the UC Berkeley News Center.

1/16/15

References

LJ Ralph, SO McCoy, K Shiu, et al. Hormonal Contraceptive Use and Women's Risk of HIV Acquisition: A Meta-Analysis of Observational Studies. The Lancet Infectious Diseases 3099(14):71052-71057. January 8, 2015.

CJ Colvin and B Harrison. Broadening the Debate Over HIV and Hormonal Contraception (Comment). The Lancet Infectious Diseases 3099(14):71076. January 8, 2015.

Other Sources

Study Supports Link Between Injectable Hormonal Contraceptive and HIV Risk. The Lancet. Media advisory. January 8, 2014.

S Yang. Study Links Birth Control Shot to Moderately Increased Risk of HIV Infection. UC Berkeley News Center. January 8, 2014.