In late October last year, the World Health Organisation (WHO) and the South African Department of Health convened a summit on Sexual and Reproductive Health and Rights — and a key issue on the agenda was the results of the ECHO trial, which came out earlier that year.
Civil society disrupted the summit proceedings, raising these concerns. Loyiso Saliso, a sexual and reproductive health advocate said: “We, as civil society […] are rejecting the ECHO results. And until there are answers to our questions with these findings we cannot move on to policy.”
The ECHO trial researchers concluded that the three-month injectable contraceptive, Depo-Provera, “did not put women at risk of HIV.” The results of the ECHO trial were greatly anticipated because, for almost thirty years, research has suggested Depo-Provera may make users more vulnerable to HIV infection.
But the interpretation of the trial’s results, as well as the manner in which the national health department engaged with the research has been a cause for concern from the start. Depo-Provera is the most widely used contraception in South Africa, and in Africa as a whole, so careful interpretation of this research design and evidence is critical.
The overwhelming majority of girl and women participants in the research were in South Africa, and others participated in Kenya, Zambia, and eSwatini. The study compared rates of HIV infection among almost 8000 girls and women using Depo-Provera, the three-month injectable contraceptive, the LNG implant, and the copper IUD. Results showed participants using all of these contraceptives experienced high-rates of HIV infection. However, when compared to the LNG implant, those taking Depo-Provera showed a higher rate of HIV infection. Despite this, the authors concluded their findings confirmed “all [contraceptive] methods [investigated] were safe and highly effective.”
WHO removes Depo risk alert
In August, the WHO removed its previous warning that Depo-Provera is not safe for women at high risk of being exposed to HIV infection. However, once the headlines had faded, critiques emerged arguing that the ECHO trial was not able to provide answers to the question of whether Depo-Provera puts women at higher risk of HIV.
For instance, the trial did not include any women who were not using contraception, or who were only using condoms. Without the inclusion of such girls and women, the study could only inform on the HIV risk of the 3-month injectable contraception when compared to either the LNG implant or the copper IUD. In other words, the trial did not produce any information on the long-standing concern about the increased risk of HIV among women using Depo-Provera, compared to those using no contraception.
Additionally, the number of participants enrolled in the trial was not sufficient to determine statistical significance of any increased risk of HIV below 50%. Indeed, the trial’s finding on the difference in risk of HIV for women using the injection, compared to women using the implant does show a higher level of risk (up to 30%). But, because this estimate is below 50%, the study’s authors conclude that this result is not significant. Yet other research has estimated that even a 20% increase in risk of HIV due to Depo-Provera use would result in a total of 13 000 new infections annually in South Africa.
Activists and researchers concern
Since the completion of the trial, members of the Local Community Advisory Board — who assisted trial researchers to liaise with the community where research took place — and research participants have voiced frustrations with the level of care provided to girls and women who became infected with HIV, or became pregnant while they were enrolled in the trial.
The scientific community has also found ethical issues with the trial. An analyst of the trial protocol and recruitment documents found that participants were recruited into the research in a manner that was coercive, and concealed the fact that the study was taking place to examine how risky Depo-Provera may be for users.
Given all of these important concerns, which raise major questions for the delivery of contraception, we welcomed the Department’s convening of the summit. We were given an opportunity to discuss the implications of the trial during the first day of the summit. Emerging from these discussions, and the strong message delivered from civil society, was the realisation that there needs to be a deep level of critical engagement with the research findings before further policy decisions are made.
The extremely high levels of Depo-Provera use, and HIV infection in South Africa demands that policymakers apply scrutiny of the evidence prior to any decisions to amend contraceptive policy and delivery. There was consensus amongst researchers at the summit that South Africa should not remove the WHO level two warning which had been in place since 2017. This warning requires healthcare providers to inform women-users that there is significant evidence showing Depo-Provera may increase risk of contracting HIV. Additionally, researchers and civil society agreed at the summit that the Department of Health should create an independent task force to critically review the ECHO findings and WHO guidelines.
However, on day two of the summit, a draft of the revised National Contraception Clinical Guidelines was shared with attendees. The document seems to suggest the Department of Health has already decided critical engagement with civil society and ECHO evidence is unnecessary. The draft recommends that women at high risk of HIV are eligible to use all injectable contraceptives, “without restriction”. The guidelines appeared to be in their final stages of completion. The only indication that this was not the final guidelines being the lack of the Director-General (at the time), Malebona Matsoso’s signature. As such, we were left wondering what the function of the summit was, if the Department of Health had already made the decision that women no longer need to be informed of the likelihood of Depo-Provera increasing HIV risk.
Self-administering Depo on the way?
Equally troubling, the guidelines also include a plan to introduce Sayana Press, a new injectable contraception produced by the pharmaceutical company Pfizer, in collaboration with the Bill and Melinda Gates Foundation. Sayana Press contains the same active ingredient (DMPA) as Depo-Provera. For the Department of Health of the country with the highest risk population of HIV in the world to introduce Sayana Press into the national family planning program without serious scrutiny of the new evidence concerning DMPA-based Depo-Provera and HIV risk shows irresponsibility and little concern for women’s rights.
Uncertainty is one of the most difficult things for researchers to communicate, because the popular understanding of science is that it generates clear answers.
But, this is a misnomer: one trial cannot generate a single straightforward answer to such a complex question. This is why we argue consideration of the cumulation of evidence is necessary to understand the relationship between HIV risk and Depo-Provera. It is essential for the Department of Health to consider the lack of evidence proving the level of HIV risk associated with Depo-Provera.
Over 30% of South African women using contraception are using the three-month injectable contraception, so the implications of any change in clinical guidelines are enormous. The state is mandated to protect women’s sexual and reproductive health rights, and therefore must prioritise the safety of South African women over any other interest. — Health-e News
Dr Catriona A. Towriss is a senior lecturer in Population Studies and Demography at the University of Cape Town. Dr Jessica Rucell is a Post-doctoral fellow at the University of Cape Town.