Women using the injectable hormonal contraceptive known by the brand name Depo-Provera have a moderately increased risk of HIV acquisition, according to a meta-analysis of 12 studies involving more than 39,500 women. Oral contraceptive pills and combined oral contraceptives did not appear to increase HIV risk. The results have attracted interest as well as calls for nuanced interpretation, while plans proceed to fund a randomized trial to fully investigate the risk.
As published in The Lancet Infectious Diseases, researchers from the University of California quantitatively summarized observational evidence from previously published studies, creating a series of pooled estimates of the effect of hormonal contraceptive use on women's risk of HIV acquisition. They found that depot medroxyprogesterone acetate (DMPA) was associated with a 40% increase in HIV risk compared with non-hormonal or no methods.
But when women deemed to be at high risk of infection (commercial sex workers and women in serodiscordant partnerships) were excluded from the meta-analysis, DMPA was associated with a 30% increase in HIV risk.
Despite widespread usage in the U.S. and abroad, some studies have suggested the injectable hormonal contraceptive might affect cervical and vaginal tissue and increase the likelihood of HIV entering the bloodstream.
However, results to date have been conflicting and inconclusive. Some studies found women who used DPMA had an increased risk of HIV acquisition, while others did not.
Accordingly, this latest study by Lauren Ralph, Sandra McCoy, Karen Shiu and Nancy Padian, which brings together existing evidence and offers a single pooled estimate of risk, has been met with some excitement from the international community.
However, AIDS Vaccine Advocacy Coalition (AVAC) Program Director Emily Bass cautions it is vital to add nuance to the headlines, while taking seriously the possibility of a link between HIV and hormonal contraception.
"The first, and arguably most crucial, thing to understand about this new paper is that it is not based on new data, or raw information," she wrote in an article published on the RH Reality Check website. "It is simply a new analysis of a set of observational studies of rates of HIV in women using different contraceptive methods. Previous systematic analyses have included all but one of these studies; last week's paper simply crunched those numbers, so to speak, in a new way."
The study's authors concede their study has several limitations.
"Meta-analyses of observational studies, like observational studies themselves, are inherently prone to bias and cannot be used to address whether the association between hormonal contraception and HIV is causal," they explain.
Indeed, Bass recommends caution when interpreting the study results.
"Like all the previous analyses, Ralph's paper worked with existing observational data, which was gathered from studies that were either not designed to specifically address the hormonal contraception-HIV link or did not randomly assign women to use a specific method," she wrote. "Observational data of this kind has inherent biases -- for example, women who choose a specific contraceptive method might also have other attributes that affect their HIV risk. ... So, although a paper like the Ralph study might be giving what looks like a precise estimate of risk associated with Depo use, it's on the basis of studies that, by definition, lack a high degree of precision."
In view of concerns about the observational evidence amassed so far, efforts are underway to fund a randomized trial to further investigate the relationship between hormonal contraception and HIV risk.
In the meantime, Ralph and colleagues encourage fellow researchers and policy makers to use the results of the meta-analysis in ongoing modeling studies to quantify the pros and cons associated with removing DMPA from the contraceptive method mix.
"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," they concluded.
So what does all of this mean for women considering their contraceptive options?
According to Bass, the decision whether or not to use DMPA remains an individual one.
"The meta-analysis isn't designed to provide guidance for individuals per se, and the authors steer clear of it," she wrote. "So we're left with existing guidance and precedent to help make practical suggestions."
Bass notes that there remains uncertainty for the individual DMPA user as far as how this particular contraceptive method might affect her risk of HIV acquisition. But there are certainly data that suggest DMPA might increase her HIV risk.
"Women who don't know their partners' status, or do know that they have an HIV-positive partner, or who have many partners and are concerned about HIV, should be using condoms, and this has always been the case," she said. "Women using Depo who fall into these categories can consider switching contraceptive methods if there is another one that is available that meets their needs -- but it is an individual choice, and there is no normative guidance (such as from the WHO) that says what the best alternative option is."
Katherine Moriarty is a consultant and freelance writer, based in Vancouver. She has 10 years of experience in the intersecting fields of public health and community development, with a focus on bloodborne virus policy and programming.