Depot medroxyprogesterone contraception may increase HIV risk

By Will Boggs MD

NEW YORK (Reuters Health) - The use of depot medroxyprogesterone acetate (DMPA) for contraception is associated with an increased risk of acquiring HIV, according to a meta-analysis of 18 studies.

"Physicians need to inform women that further research is needed to better understand the possible link between depot-medroxyprogesterone acetate and an increased risk of HIV acquisition," Charles S. Morrison, from FHI 360, Durham, North Carolina, told Reuters Health by email. "And, because of this, women need to be strongly encouraged to use condoms during sex and use other HIV preventive measures."

Whether hormonal contraception increases the risk of HIV acquisition remains controversial, with some studies showing an association and others showing no such link.

Morrison and colleagues used individual participant data on 37,124 women in 18 studies (9 cohorts, 9 randomized controlled trials) to assess the risk of HIV acquisition associated with combined oral contraceptives, DMPA, and norethisterone enanthate (NET-EN).

The overall incidence of HIV infection was 4.2 per 100 woman-years.

While there was no association between combined oral contraceptives and HIV acquisition, DMPA was associated with a significant 50% increased risk, and NET-EN use was associated with a borderline 24% increased risk.

In direct comparisons, DMPA was associated with a 43% higher risk of HIV acquisition than combined oral contraceptives and a 32% higher risk than NET-EN. NET-EN use was associated with a borderline-significant 30% increased risk compared with combined oral contraceptives (p=0.055).

The results were reported January 22 online in PLOS Medicine.

"The associations between hormonal contraception and the risk of acquiring HIV infection were attenuated in studies that had a lower risk of methodological bias compared to those with higher risk of bias," Dr. Morrison noted. This suggests, he said, that some of the risk may be due flaws in the studies - and points to the need for a randomized clinical trial.

"Such research has the potential to provide the robust evidence that will allow policy makers, clinicians, and individual women to make well-informed decisions about hormonal contraception in areas of high HIV prevalence and incidence."

"It is critical to ensure that women who are at high risk of HIV are aware that, while some studies have indicated that using DMPA may place them at greater risk of acquiring HIV infection, other studies have not shown that, and that it is important to use condoms during sex and take other HIV-prevention measures," Dr. Morrison concluded.

"The findings of this study, as well as our own meta-analysis, suggest that use of DMPA is associated with an elevation in risk of HIV acquisition," Dr. Lauren Ralph, from the University of California, Berkeley, told Reuters Health by email.

But importantly, she added, "whether this increased risk for DMPA merits its withdrawal or scale-back needs to be balanced against the known benefits of this method, including its important role in preventing unintended pregnancy and its associated morbidity and mortality."

"Given these benefits, the magnitude of risk observed in our study and Dr. Morrison's would likely not merit withdrawal of DMPA in most settings worldwide, especially among women considered to be at lower risk for HIV," Dr. Ralph said.

"Dr. Morrison's conclusion that the proposed randomized trial would offer more 'definitive evidence' is not universally supported, given concerns that a trial on this topic will be faced with numerous and perhaps insurmountable methodological and ethical challenges," Dr. Ralph said. "Even if the trial does move forward, its results will not be available for many years. In the short term, we need to focus on other policy solutions such as expanding contraceptive options for women and facilitating availability and uptake of other highly effective methods such as long acting, reversible methods."

Dr. Chelsea Polis, from Guttmacher Institute, New York, has also explored the association between hormonal contraceptives and HIV acquisition. She told Reuters Health by email, "Physicians should be aware that scientific uncertainty persists with regard to whether use of DMPA is causally associated with an increased risk of HIV acquisition in women."

Her recent systematic review concluded, "Women choosing progestin-only injectable contraceptives such as DMPA or NET-EN should be informed of the current uncertainty regarding whether use of these methods increases risk of HIV acquisition, and like all women at risk of HIV, should be empowered to access and use condoms and other HIV preventative measures."

"Women urgently need access to safe, effective, acceptable products that can help them simultaneously prevent unintended pregnancy and various sexually transmitted infections, including HIV," Dr. Polis concluded. "Development of multipurpose prevention technologies would be a critical step in expanding women's prevention options and should be prioritized on the global health agenda."

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health Development and the Bill and Melinda Gates Foundation. Senior author Nicola Low is a member of the PLoS Medicine editorial board; no other authors report any disclosures.

SOURCE: http://bit.ly/1Lf9sXS

PLOS Medicine 2015.

(c) Copyright Thomson Reuters 2015. Click For Restrictions - http://about.reuters.com/fulllegal.asp