In October,Â The Lancet Infectious DiseasesÂ published a study by Renee Heffron and colleagues suggesting that HIV-negative women using hormonal contraception (HC) might be at increased risk for HIV infection. The study also suggested that HIV-positive women using HC might be at increased risk of transmitting HIV to an uninfected male sexual partner. These new findings will be a topic of conversation at the 2011 International Conference on Family Planning later this month in Dakar, Senegal.
Chelsea Polis is an epidemiologistÂ atÂ USAID who received her PhD in reproductive health from theÂ Johns Hopkins Bloomberg School of Public Health (JHSPH)Â in 2009, and holds an associate faculty appointment in the JHSPHÂ Department of Epidemiology. Working with colleagues at CDC and WHO, Polis is leading two systematic reviews of the evidence to address HC and HIV risk. She offered her perspectives in the following emailed Q&A.
Should women reconsider their HC use in light of this study?
No; at this time, women need not reconsider their HC use in light of this study alone. For the time being, USAID and WHO have not recommended any change to current contraceptive guidelines. Careful evaluation of the Heffron study is underway. This study has several strengths, but also has limitations that complicate the ability to draw definitive causal inference between HC and HIV risk. In addition, previous studies have found inconsistent results. The scientific community is intently focused on understanding and incorporating new evidence in a thorough but rapid manner, and is working to establish consensus on interpretation of the new findings.
It remains critical that known risks and benefits of various contraceptive methods are clearly communicated. If it is ultimately determined that HC increases HIV risk, this will need to be communicated. People should also be informed that HC is not intended to protect against HIV or other sexually transmitted infections (STIs), and that dual protection against unintended pregnancy and STIs/HIV may be achieved by using condoms along with a highly effective contraceptive method.
Why is HC use important, particularly in settings of high HIV risk?
HC methods are highly effective at preventing pregnancy, and are among the most commonly used contraceptive methods in sub-Saharan Africa. Unintended pregnancy is associated with multiple adverse outcomes, including maternal and infant mortality. HIV-positive women report high rates of unintended pregnancy, and helping these women access voluntary contraceptive services could contribute to reductions in perinatal HIV. Furthermore, unanswered questions remain with respect to the relationship betweenÂ pregnancyÂ and risk of HIV acquisition in women and transmission to men. Competing risks must be carefully considered.
What do current guidelines suggest with respect to use of HC by women at risk of or living with HIV?
WHO continually updates theÂ Medical Eligibility Criteria for Contraceptive UseÂ (MEC), which encapsulates the latest data into clear recommendations for use by policy-makers, family planning program managers, and the scientific community. The 2009 MEC suggests no restrictions on use of hormonal contraceptive pills, injections, implants, patches, or rings for women at risk of or living with HIV. Women on antiretroviral therapy (ART) should confirm that no drug interactions are expected with HC for their regimen. Women with AIDS who are not clinically well on ART typically should not undergo IUD insertion, whether hormonal or non-hormonal. However, women with HIV and those who are clinically well on ART can generally use hormonal or non-hormonal IUDs. In general, hormonal methods are currently considered to be safe for most women, regardless of their HIV risk or status.
How will findings from the Heffron study be incorporated into global guidance?
The World Health Organization (WHO), in collaboration with USAID and other partners, will convene a meeting of a multi-disciplinary group of experts in January 2012. This technical consultation will seek scientific consensus on the Heffron study and other new studies, and assess whether the current WHO recommendations for contraceptive use among women at risk of or living with HIV remain consistent with the current body of evidence.
What are the strengths and weaknesses of the Heffron study?
The Heffron analysis has several strengths, including the fact that they prospectively collected detailed information at frequent follow-up visits, and analyzed a large population of HIV serodiscordant couples in multiple countries. The majority of previous studies have only analyzed women, without having information on partner HIV status. The study also used multiple statistical techniques to attempt to control for confounding. The investigators measured not only actual HIV seroconversions, but also assessed for differences in genital viral shedding by HC status, as a potential biological mechanism for female-to-male HIV transmission.
This study also has several limitations. It was not originally designed to examine if HC impacts the risk of HIV. Women self-selected their contraceptive method (if any), and HC users may have higher coital frequency, lower condom use, and less consistent condom use (and therefore, greater exposure to HIV) than non-users of HC. Though the investigators attempted to control for confounding, statistical adjustment may not be able to adequately account for such differences. Adjustment for sensitive behaviors like unprotected sex may be particularly complicated, since this uses self-reported information of unknown accuracy, and inadequate measurement can lead to inadequate adjustment. In addition, although the investigators theorized that the increased genital viral shedding seen among injectable users could explain the doubling in risk of HIV transmission to men, previous studies suggest that over five times that amount of genital shedding would generate only a 67% increase in risk of HIV transmission. So, it is unclear if the observed differences in shedding could explain the increased risk of female-to-male transmission, or whether other potential explanations might explain these findings.
Could there be differences between HC users and non-users that some studies do not adequately account for?
In any observational study, the potential for unmeasured or residual confounding is always a concern. As one example, Iâ€™ve been thinking a lot about potential differences in both the level andÂ qualityÂ of condom use between HC users and non-users, and whether various study methodologies adequately address these concerns. We know HC users in many populations are less likely to use condoms, but among those that do, theÂ qualityÂ of condom use might also be different than in women who donâ€™t use HC but do use condoms. HC users already have an effective method of contraception, so if they use condom, they are more likely used to prevent HIV/STIs. Non-users of HC might use condoms for pregnancy prevention, or for HIV/STI prevention, or both. Some studies suggest that condom use is more consistent when used for pregnancy prevention than when used for infection prevention. Consistent condom use is associated with reduced risks of HIV, but oftentimes, inconsistent condom use is not. Also, women using condoms to prevent infection might use them with men perceived as â€œhigh-risk,â€ whereas condoms for contraception would likely be used with any fertile partner, including â€œlow-riskâ€ partners. So, although some observational studies do attempt to adjust for condom use differences between HC users and non-users, adjusting for â€œanyâ€ condom use may not capture potential differences in consistency of use or partner risk. Comparing findings of studies by how they addressed condom use does seem to suggest some potentially interesting patterns.Â Â However, this body of evidence is extremely complicated, and we will be considering condom use and many other factors in the systematic reviews. Our ultimate goal is to provide accurate, unbiased, comprehensive, and up-to-date information on the risks and benefits of HC, in order to help individuals around the world make voluntary, well-informed decisions about their reproductive health.