Recently published research suggests that use of hormonal contraceptives, particularly injectables, may double the risk of HIV (see K4Health blog, October 7, 2011). On October 20, 2011, a global teleconference took place to give advocates, researchers, and policy makers an opportunity to discuss this research and its implications.
Sponsored by AVAC (Global Advocacy for HIV Prevention), the teleconference included study investigators Dr. Jared Baeten and Renee Heffron of the University of Washington in Seattle, Washington, USA, and Dr. Helen Rees of the University of Witwatersrand in Johannesburg, South Africa. Also on the teleconference were Dr. Mary Lyn Gaffield, Scientist at the World Health Organization (WHO), and Dr. Charles Morrison, Senior Epidemiologist at FHI 360.
Baeten emphasized that “this kind of international discussion is important…to put the findings into perspective.” After a brief recap of the findings, originally published in The Lancet Infectious Diseases
, the speakers answered several critical questions that have been raising concern in the international public health community.
Do the study findings pertain to hormonal contraceptives in general, or to injectables or oral contraceptives specifically?
Although the primary analysis of the study was among women using any hormonal contraceptive method compared with women not using a hormonal method, Baeten explained that the data came largely from injectable users. “Most interpretations of the study have focused on HIV risk associated with injectable use. I think that’s the best interpretation,” stated Baeten. Because there were few study participants who used oral contraceptive pills, the study could not make a reliable estimate of HIV risk among pill users. Baeten speculates that the study findings are probably most relevant to the DMPA injectable because it was the most common injectable used in the countries where the study was conducted.
How do the recent findings compare with findings from previous research on DMPA use and HIV risk?
Putting the new study findings into historical perspective, Charles Morrison explained that 5 of 14 prospective studies have found a statistically significant risk of HIV with use of DMPA injectables. However, more of the studies showed no increased risk with DMPA use. Furthermore, the studies that did find an increased risk of HIV tended to be among populations at high risk of HIV, such as sex workers—but this was not always the case. In summary, Morrison maintained that the evidence to date has been mixed, which, he argues, points to the need to design a more definitive randomized controlled study.
What about pregnancy itself being a risk factor for HIV?
Helen Rees summarized findings from a parallel study
that found that pregnant women who were infected with HIV were two times more likely to transmit the infection to their uninfected male partners than non-pregnant women with HIV. While Morrison pointed out that the body of evidence on pregnancy and HIV risk also show mixed results, Rees expressed:
What this means programmatically is that, if we accept the data, you’ve got a bit of a problem because on the one hand it would appear from this data that DMPA increases the risk of HIV acquisition. On the other hand, if women stop using these methods and get pregnant then their risk of HIV acquisition is also increased…you’ve got quite a dilemma for HIV if you accept these data.
Can research ever put this issue to rest?
Morrison argues that the research community needs to conduct a randomized controlled trial—where women would be randomly assigned to use either a hormonal or nonhormonal contraceptive method—in order to get a definitive answer to the question of whether hormonal methods increase HIV risk.
Such a trial would be expensive, possibly requiring multiple funders. Morrison explained that the study would have to include approximately 3,200 women in order to be able to detect about a 40% decrease in HIV acquisition in the comparison group (nonhormonal method users).
Furthermore, there are questions about whether women would agree to be randomized to use a certain contraceptive method and about how likely they are to continue using that method for an extended time. In a pilot study
in Brazil, Egypt, Guatemala, and Vietnam, researchers from FHI 360 showed that many women would indeed agree to be randomized, as long as the various methods were close in their level of effectiveness.. After screening 555 women, 368 agreed to be randomized to use either a copper IUD or the DMPA injectable, and 68% of them were still using their assigned method after 12 months of follow-up. In a separate feasibility study
, 70% of women surveyed said they would take part in a future randomized trial and would accept being randomized to using either an IUD or DMPA.
But is it ethical to conduct any further research on this issue given that some studies have shown an increased risk of HIV with hormonal method use?
Baeten contends that “there’s enough disagreement in published studies today and consternation in the field that continuing to analyze existing data sets and considering the design of a randomized controlled trial is really important.” This will be a point of discussion at the forthcoming expert technical consultation that WHO is convening in January 2012
FHI 360 is conducting a meta-analysis using data from many existing relevant studies. Results of that analysis should be published in about a year, Morrison explained. He made it clear, however, that while the meta-analysis might be able to shed more light on the question, it would not necessarily provide a definitive answer because the analysis will still be among observational studies.
What comes next in terms of the WHO process?
Mary Lyn Gaffield explained that the planned January 2012 WHO meeting will be among HIV and family planning researchers and programmers; pharmacologists; experts in health policy, reproductive biology, and immunology; and patient advocates. These experts will consider the body of evidence synthesized by WHO related to the safety of using hormonal contraceptives among women with HIV and women at risk of HIV.
Morrison remarked that one important question that the expert group needs to address is whether providers should tell women that if they use DMPA, they may be at increased HIV risk. “If we think that’s really true, that they may be…then aren’t we under duty to tell women this?” asked Morrison. Recognizing that practitioners with program experience may think that it will be too difficult for providers to communicate this information effectively to women, Morrison emphasized that this issue needs input by both scientists and program planners and managers.
Chaired by methodologists in guideline development, the group will come to a consensus about whether current WHO recommendations should remain the same or change. WHO plans to issue a statement within a week of the expert meeting.
Current WHO recommendations
indicate that all hormonal methods are safe to use among women with HIV and women at risk of HIV (category 1; no restriction for use of the method).
What do we do now, in the absence of a randomized controlled trial or the WHO expert consultation?
Responses from the speakers included emphasizing the importance of integrating family planning and HIV services, counseling women about dual method use for protection against both pregnancy and HIV, developing new contraceptive methods, and expanding the available contraceptive method mix in countries. Speaking about the experience in South Africa, Rees expressed:
What we are saying in South Africa at the moment…is we recognize the limitations of this data, that these are observational studies, and that they don’t all show the same sorts of trends. However, we do recognize that what you might describe as the better studies tend to be going in the direction of possible harm, particularly with DMPA. But the problem is at the moment, it’s not strong enough to say this is definitely an issue. So we’re taking a slightly different approach. What we’re saying is that the method mix in South Africa has become too narrow. Women have become very, very limited to choice, between injectables and pills. The IUD has almost fallen away. We’re not promoting condoms enough...and we haven’t introduced anything like implants in the public sector…What we want to do as a matter of urgency is once again expand the choice of contraceptives available, so we would reinstitute the copper IUD, we would introduce lower dose hormonal methods that don’t have the great peak of hormones that you see with Depo-provera, and then over time…consider the phasing out of the long-acting progestin injectables. If over time, with something like a randomized controlled trial, you didn’t demonstrate harm from these methods, then we wouldn’t have to do that, but what we would have done is increase the method mix available.
Ruwaida Salem is Senior Technical Writer at the Knowledge for Health Project.