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AIDS 2014: More Data Suggest Increased HIV Risk from Injectable Contraceptives

A sophisticated meta-analysis, pooling individual-level data on 37,000 women, has found that the use of DMPA injectable hormonal contraception is linked with a higher rate of new HIV infections among women, researchers reported at the 20th International AIDS Conference last week in Melbourne. However, the World Health Organization (WHO) announced at the same session that its guideline supporting the provision of this contraceptive to women at risk of HIV infection remains unchanged.

[Produced in collaboration with Aidsmap]

WHO reviewed research on the issue on contraception and HIV acquisition earlier this year, concluding that the data that were available at the time did not support restrictions on the use of injectable contraceptives, and agreed in a new version of its guidance released just prior to the conference. However, the agency could not take into consideration the meta-analysis released at AIDS 2014 nor a number of new studies that are expected to issue findings within the next year. WHO's guidance will likely need to be reconsidered when those data are available.

The potential for some hormonal contraceptives to raise a woman's risk of HIV infection has been the subject of scientific debate for several years. Around half of the available studies suggest an increased risk, but the other half do not. Moreover, accurately assessing associations between contraceptive use and HIV infection with data from observational studies is challenging and analytically complex. Studies have used inconsistent approaches and generated a body of evidence that is complicated and difficult to interpret.

Furthermore, HIV is not the only consideration when it comes to contraceptive use. The broader health impact of fewer women using effective long-acting contraceptives could be significant. In settings where maternal mortality is high due to complications of pregnancy and childbirth, effective contraception contributes to better health outcomes for women. Infants of mothers who die in childbirth have poorer health outcomes, and closely spaced pregnancies contribute to infant mortality.

Charles Morrison of FHI 360 presented the results from the meta-analysis, which aimed to determine whether the use of specific hormonal contraceptives increases the risk of HIV acquisition compared to women not using hormonal contraception or using a different form of contraceptive.

Most meta-analyses take the overall results from previously published research and combine each study's results. The figures used are "aggregate data" -- the overall average or estimate derived from each study.

In contrast, this was an individual participant data meta-analysis, a more sophisticated and complex approach. It involved collecting the raw data on all individual study participants from the original researchers and pooling it. This ensures greater consistency in the way the data are analyzed (e.g., attention to confounders) and a greater ability to analyze the findings for different subgroups of participants.

The analysis included 18 prospective observational studies, with data from a combined total of 37,124 women. All were conducted in southern or eastern Africa.

Reported contraceptive use included 28% using the injectable depot medroxyprogesterone acetate (DMPA or Depo Provera), 8% using the injectable norethisterone enanthate (NET-En or Noristerat), 19% using a combined oral contraceptive pill, and 43% not using any form of hormonal contraceptive.

A total of 1830 women acquired HIV while taking part in a study.

Compared to non-users, women using DMPA had an elevated risk of infection (hazard ratio [HR]1.56; 95% CI 1.31-1.86), as did women using NET-En (HR 1.51; 95% CI 1.21-1.90). There was no increased risk for women using oral contraceptives.

Similarly, comparing women using injections with those using oral contraceptives, there was an elevated risk associated with DMPA (HR 1.43; 95% CI 1.23-1.67) and NET-En (HR 1.30; 95% CI 0.99-1.71).

The results were consistent in several subgroup and sensitivity analyses. However, when only studies that were judged to be methodologically more reliable were included, the increased risk appeared smaller.

Morrison did not use thee findings to argue for a restriction on the use of injectable contraception in settings with a high prevalence of HIV. He acknowledged the limitations of all observational data and argued that what is needed is a well-conducted randomized controlled trial -- something he is seeking funding for.

Mary Lyn Gaffield of the World Health Organization outlined WHO's latest recommendations on contraception and HIV, based in part on a systematic review conducted earlier this year and recently published in the journal Contraception.

That review identified 9 studies described as "informative," but with important methodological limitations. While 5 found that injectable contraceptives have no impact on HIV infection, 4 suggested hazard ratios ranging from 1.48 to 2.54 -- or nearly 3-fold higher risk.

Gaffield said that the epidemiological data did not warrant a change to WHO's guidance that DMPA and NET-En be available, without restriction, in areas of high HIV prevalence.

Nonetheless, the guidance states: "Women at high risk of HIV infection should be informed that progestogen-only injectables may or may not increase their risk of HIV acquisition. Women and couples at high risk of HIV acquisition considering progestogen-only injectables should also be informed about and have access to HIV preventive measures, including male and female condoms."

In relation to other methods of hormonal contraception, the WHO guidance does not recommend restrictions for women at risk of HIV or women living with HIV. Intrauterine devices (IUD) with progestogen can generally be used, but initiation should usually be avoided if women have advanced or severe HIV disease.

The review examined the data on contraception and HIV transmission from women to men, as well as on contraception and HIV disease progression, and did not find convincing evidence of increased risks.

For women taking antiretroviral therapy, the guidance says they are generally able to use hormonal contraception. However, due to potential drug interactions, the document outlines some considerations when taking efavirenz (Sustiva or Stocrin), nevirapine (Viramune), and some protease inhibitors.

7/29/14

References

C Morrison, P-L Chen, C Kwok, et al. Hormonal contraception and HIV infection: results from a large individual participant data meta-analysis. 20th International AIDS Conference. Melbourne, Australia, July 20-25, 2014. Abstract THAC0503.

ME Gaffield, SJ Philips, RC Baggaley, et al. HIV and contraception – complex issues for safe choice: the latest recommendations from the World Health Organization (WHO). 20th International AIDS Conference. Melbourne, Australia, July 20-25, 2014. Abstract THAC0505LB.

CB Polis, SJ Phillips, KM Curtis et al. Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence. Contraception. July 22, 2014 (Epub ahead of print).