Geneva, Switzerland — 13 June 2019
A large clinical research study conducted in four African countries found no significant difference in the risk of HIV infection among women using one of three highly effective, reversible contraceptive methods. Published in The Lancet on 13 June 2019, the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial resolved decades of uncertainty about whether progestogen-only injectable contraceptives increase women's susceptibility to HIV — but its findings on the alarmingly high background HIV incidence among participants were equally consequential.
The study, carried out in Eswatini, Kenya, South Africa, and Zambia, enrolled 7,829 sexually active HIV-negative women aged 16 to 35 years who wanted to use a modern method of contraception. Participants were randomly assigned to one of three methods: DMPA-IM (intramuscular depot medroxyprogesterone acetate, a three-monthly progestogen-only injectable), a copper-bearing intrauterine device (IUD), or a levonorgestrel (LNG) implant.
Resolving Decades of Uncertainty
Over the past 25 years, as the HIV epidemic took hold in many countries, a number of observational research studies suggested a possible increased risk of HIV acquisition for women using progestogen-only injectables, particularly DMPA-IM. Because of limitations in the design of these studies, it was not possible to determine whether HIV infections were due to the type of contraceptive method used or other confounding factors. The ECHO trial was designed specifically to address this question with the rigour of a randomised clinical trial.
Among the 7,829 women who took part in the study, 397 HIV infections occurred over the follow-up period. There was no statistical difference in the rate of HIV acquisition among the women using the three methods:
| Contraceptive Method | HIV Infections | Key Characteristics |
|---|---|---|
| DMPA-IM (injectable) | 143 | Three-monthly progestogen-only |
| Copper-bearing IUD | 138 | Non-hormonal, lasts 10–12 years |
| LNG implant | 116 | Progestogen-only, lasts up to 5 years |
Reassuring on Contraception, Sobering on HIV
The results on the contraceptive safety question were reassuring. All three methods demonstrated high levels of safety and effectiveness in preventing pregnancy, and all were well-accepted by the women using them. By providing high-quality randomised evidence, the ECHO trial helped resolve decades of uncertainty, allowing health organisations including WHO to affirm that women should have access to a full range of contraceptive options without fear of increased HIV risk.
However, the findings on HIV incidence were sobering. Professor Helen Rees, Executive Director of the Wits Reproductive Health and HIV Institute at the University of the Witwatersrand in Johannesburg, and a member of the five-person ECHO Management Committee, stated: "After decades of uncertainty, we finally have robust scientific evidence about the potential relationship between hormonal contraception and the risk of HIV from a rigorous randomized clinical trial. The results on this question are reassuring, but our findings are also sobering, because they confirm unacceptably high HIV incidence among young African women."
WHO Response and Next Steps
Dr. James Kiarie, from the Department of Reproductive Health and Research at WHO, stated: "These results support making available to women and girls a broad choice of effective contraceptive methods that empower them to make informed decisions about their own bodies — including if and when to have children. Better access to contraception and quality reproductive health services would have a dramatic impact in improving the lives of millions of women and their families."
Dr. Rachel Baggaley from WHO's HIV and Hepatitis Department added: "The study highlights the need to step up HIV prevention efforts in these high-burden countries — particularly for young women. These should include providing HIV testing and a range of HIV prevention choices within contraceptive service programmes."
Following its standard practice when important new research findings are published relating to contraceptive safety, WHO convened a Guideline Development Group to review its existing recommendations concerning women's eligibility for using various contraceptive methods if they are at high risk of HIV. Updated recommendations were issued by the end of August 2019.
The Call for Integrated Services
The high incidence of HIV reported in the trial is above the WHO suggested threshold for offering PrEP, which the organisation recommended should be considered in countries where the incidence of HIV is above 3%. The trial reinforced the need to strengthen HIV prevention integration within contraceptive and other sexual and reproductive health services, including HIV testing, linkage to antiretroviral therapy for those testing HIV-positive, partner testing, condom promotion, and PrEP.
Yvette Raphael, a member of the Global Community Advisory Group for the ECHO Study, offered a pointed critique: "Regardless of the data from the ECHO trial, the limited choice of contraceptives that women have is not OK. We hope that this result will prompt action and put women first. Women want more options beyond DMPA."
Currently, 214 million women in developing countries want to avoid pregnancy but do not use a modern contraceptive method. The ECHO trial's findings support continued access to all three methods studied by all women, including those at high risk of HIV infection, while underscoring the urgent need to expand the range of available contraceptive options and to integrate comprehensive HIV prevention into family planning services.
Study Design and Conduct
The ECHO study was conducted between 2015 and 2018 across 12 sites in four countries with settings of high HIV incidence. All women who participated received ongoing health services, including counselling on HIV prevention and care, and screening and treatment for sexually transmitted infections. The trial was carried out by a consortium led by FHI 360, the University of Washington, the Wits Reproductive Health and HIV Institute, and the Human Reproduction Programme (HRP) at WHO.
The World Health Organization and the Human Reproduction Programme acknowledged and thanked the 7,829 women and their communities for their participation, without which the understanding of the safety of three highly-effective contraceptive methods would not have been possible.
Sources
- WHO Departmental Update: New study finds no link between HIV infection and contraceptive methods, 13 June 2019.
- The Lancet: Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, 13 June 2019.
- Wits Reproductive Health and HIV Institute: ECHO Study Results Release.
- ICAP at Columbia University: ECHO Trial findings, July 2019.
- UNAIDS Joint Statement on the ECHO Study, 14 June 2019.
FIRAT Editorial Board
Institutional Research Desk · Foresight Institute of Research and Translation
The collective editorial and research translation board of FIRAT, synthesising peer-reviewed evidence, policy briefs, and division milestones across our seven foundational research pillars.
