A clinical trial known as Evidence for Contraceptive Options and HIV Outcomes (ECHO)—originally designed to answer important questions about possible connections between risk of HIV infection and the use of non-barrier hormonal contraceptives—now hangs in the balance because of a funding shortfall. For women in countries and communities with limited contraceptive choices and high rates of HIV, particularly in sub-Saharan Africa, this is an unacceptable development.
Women make up more than half of all people living with HIV worldwide, and they continue to bear the burden of new infections. Incidence rates vary by age and country, but remain unacceptably high in the context of comprehensive, state of the art prevention services. (As one example, in the VOICE trial of women’s HIV prevention options, overall incidence was nearly 6 percent.) HIV incidence rates are particularly high in adolescent girls and young women, and globally HIV is the leading cause of death of women of reproductive age. The same women who are most at risk of HIV are also in need of a variety of reliable methods of contraception—a glaringly unmet need in sub-Saharan Africa, where fewer than 20 percent of women use a modern contraceptive method.
For those women in sub-Saharan Africa who do have access to contraception, the majority use a hormonal method (an injectable or the oral contraceptive pill). Of these women, 60 percent use a long-acting injectable such as Depo or, less frequently, NET-EN. This prevalence of these methods does not accurately reflect women’s preference since in many settings, Depo is one of a limited number of options for women—and often the only long-acting, discrete method (versus a daily contraceptive pill). Expanding the range of available choices is another key policy and advocacy priority, in sub-Saharan Africa and around the world, including in the United States.
Contraception not only allows women to determine when and how often they become pregnant, it also saves their lives. Risk of maternal morbidity and mortality—already unacceptably high in many parts of the world—rises even more in the context of unplanned pregnancies. Lack of access to effective contraception is a health and human rights issue that cannot be ignored.
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At the same time, there are persistent questions about whether some contraceptive methods, particularly long-acting injectables like Depo, increase women’s risk of acquiring HIV. These questions arise from observational data. Some studies suggest that Depo does increase risk, while others do not. This is precisely the question that the ECHO trial is designed to answer.
According to the ECHO trial team, which has briefed civil society, it would cost roughly $60 million to conduct the ECHO trial—clearly a minimal investment when compared to the economic, social, and public health costs of HIV and AIDS, unplanned pregnancies, and maternal death and illness across sub-Saharan Africa. In fact, the ECHO trial seeks to answer a question raised 25 years ago: Do contraceptive methods, particularly hormonal contraceptive methods, increase women’s risk of HIV acquisition? The answer to this question is long overdue, and the lack of investment in such research reflects a lack of strategic and financial priority for a critical women’s health and rights question.
In discussing the trial, and other approaches to the current uncertainty, stakeholders have asked why the data are mixed, and whether it’s possible to gain clarity with the information available and/or with basic science studies. The main limitation of all of the existing data on both injectables and pills and potential HIV risk is that they come from observational trials that were not designed to answer the question directly. Confounding factors cannot be controlled for, and many trials rely on women’s self report about the method they were using. There simply aren’t enough women in sub-Saharan Africa using other strategies, like the implant or the intrauterine device, to gather even observational data. The existing information is, therefore, difficult to interpret, and leave unanswered critical questions that affect the lives and health of women who have urgent needs to both space or limit births and to protect themselves from HIV. The ECHO trial is designed to help answer these questions directly for Depo, the implant (Jadelle), and the copper intrauterine device—methods about which there are even less data. It has the potential to provide more definitive, actionable information than basic science research.
The ECHO trial is the type of research we have been waiting for, with great anticipation, since a 2012 World Health Organization (WHO) review of the existing data on hormonal contraceptives and HIV risk. In this review and in an update in July 2014, research is a clear priority. The document states, “WHO strongly supports the need for further research to identify definitive answers to these issues.”
ECHO was proposed to meet this identified need. It is a randomized clinical trial that would look at whether the three options—Depo, Jadelle, and the copper intrauterine device—affect HIV-negative women’s risk of acquiring HIV.
Advocates for HIV-positive women, HIV prevention advocates, and sexual and reproductive health advocates have been following this issue closely. We are united in the conviction that women should be fully informed in their contraceptive choices and that we should not have to choose between HIV prevention and safe and effective contraception. We are also united in the need to broaden the range of contraceptive options available and accessible to all women—in the context of complete data about their risks and benefits.
The concerns related to HIV risk have to be considered in the context of the health risks of pregnancy, particularly unintended pregnancies. Epidemiologists have calculated the new HIV acquisitions that might be attributable to Depo, in the event that it does increase risk, and the rates of maternal deaths and live births that would occur if Depo were to be withdrawn, without an immediately acceptable and accessible replacement. In both instances, the greatest impact on women is in east and southern Africa.
Given the level of maternal death and illness, not to mention other public health outcomes of unintended pregnanciesy, an increase in risk of HIV acquisition by users of Depo must be weighed against the risks associated with unintended pregnancies. But context does not mean conflict—and the urgent need for a mix of effective contraceptive methods does not outweigh the need for clarity about how methods affect women’s risk of HIV acquisition. No one wants to swap illness and death associated with HIV acquisition for pregnancy-related morbidity and mortality.
And, indeed, no one is advocating for Depo to be removed without providing affordable, accessible alternative contraceptives. But the status quo cannot stand because of the challenges ahead. Current WHO guidance on Depo states that “women at high risk of HIV infection should be informed that progestogen-only contraceptives may or may not increase their risk of HIV infection.”
Not only is the message confusing, but it is also incredibly challenging for those working in public health clinics to communicate. Without the ECHO trial, this confusing message will continue being given to women currently using or initiating Depo—if they receive any message at all. Even as other methods, such as the contraceptive implant, gain popularity in some regions, some women will still only have access to Depo and they will still be told “this might increase your risk; it might not”—unless a trial like ECHO takes place.
Unfortunately, the international funding community has not adequately committed to this research. Even before the current ECHO protocol was put on hold, it had already been scaled back once due to budget concerns. This trial design should be driven by scientific questions and women’s needs, not funding.
We call on the donors to ensure the trial is fully funded without additional budget cuts or delays. We call on funders who have stepped up to date, including the Bill & Melinda Gates Foundation, USAID, the South African government, the South African Medical Research Council, the Wellcome Trust, and the UK Medical Research Council to maintain and/or expand on existing funding commitments. We challenge the U.S. National Institutes of Health and the European & Developing Countries Clinical Trial Partnership to confirm their partnership with and support for this research. And we urge these funders to work together to undertake vigorous advocacy that bridges the HIV and contraceptive research agendas. Each of these organizations have spoken about the need to promote women’s health and now they must invest in doing so. The amount of funding needed is minimal compared to investments in many other HIV prevention trials. These price tags reflect vastly different research questions and infrastructure requirements—however the point remains that this is a relatively small investment to answer a question of enormous importance.
Some funders, scientists, and advocates have raised issues about whether the trial is necessary or feasible. One argument is that the world can go ahead and increase method mix, moving away from Depo and toward other methods, without the ECHO trial. This would mean expanding access to other hormonal methods without any additional information about their relationship to HIV. The question about whether the trial is feasible—whether women will enroll, accept randomization, remain on methods, and so on—is valid, and can only be answered by attempting the trial. ECHO investigators say the research would be implemented with monitoring that would gauge feasibility in real time—allowing the trial to be stopped or altered if it was necessary.
Although concerns about the trial are fair, a $60 million investment in this set of questions is one of the best research investments that could be made in reproductive health and rights in the context of women and HIV today. As women in all our diversity, this advocacy—and the clarity it can engender about our contraceptive choices—is long overdue. Women at risk of HIV deserve to know whether their choice of contraception affects their chances of acquiring HIV. Now is no time to turn back.