EXECUTIVE SUMMARY

Results from a large, randomized trial among African women found no substantial difference in HIV risk using the copper intrauterine device (IUD), the levonorgestrel implant, and the depot medroxyprogesterone acetate (DMPA) injection.

  • The data counter research that suggested a potential association between some types of contraceptives and risk of acquiring HIV.
  • The World Health Organization (WHO)’s Guideline Development Group will consider the most recent research on contraception and HIV risk, and determine whether any changes are needed for the WHO’s Medical Eligibility Criteria, which serves as global guidance on contraceptive use.

Results from a large, randomized trial among African women found no substantial difference in HIV risk using the copper intrauterine device (IUD), the levonorgestrel implant, and the depot medroxyprogesterone acetate (DMPA) injection.1 The data counter research that suggested a potential association between some types of contraceptives and risk of acquiring HIV.

According to the World Health Organization (WHO), more than 150 million women worldwide use various hormonal contraceptives, including progestin-only contraceptives such as injectables, for family planning. In sub-Saharan Africa, progestin-only injectable contraceptives are the most commonly used method.

As the HIV epidemic took hold in many countries over the last 25 years, observational studies began to explore whether hormonal methods affected the risk of HIV. Evidence from 13 observational studies of DMPA, norethisterone enanthate, or nonspecified progestin-only injectables suggested some association between use of progestin-only injectables and risk of HIV acquisition; however, it was unclear whether results stemmed from a causal relationship or methodological limitations.2

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) study investigated the comparative HIV risks and pregnancy prevention benefits associated with the use of hormonal contraceptives. It included results from 7,829 women ages 16-35 years in East and Southern Africa. The research consortium was led by Durham, NC-based FHI 360, the University of Washington, Wits Reproductive Health and HIV Institute in Johannesburg, South Africa, and the WHO. Results were presented at the June 2019 South African AIDS Conference in Durban, South Africa.

“The ECHO Study has successfully addressed a long-standing public health question, providing high-quality evidence on the relative risk of HIV acquisition with use of three effective contraceptive methods,” says Timothy Mastro, MD, FACP, DTM&H, Chief Science Officer at FHI 360, and ECHO management committee member. “The results support continued access to the three contraceptives studied.”

The study addressed “deep concerns” that DMPA, in particular, was associated with higher transmission rates for HIV, says Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA.

The findings are important, especially in resource-poor areas like sub-Saharan Africa, where DMPA is the most effective available option for birth control, notes Nelson.

Look at Study Design

The ECHO study began enrollment in December 2015, following 7,829 sexually active, HIV-negative women ages 16-35 years across 12 clinical trial sites in Eswatini, Kenya, South Africa, and Zambia. While women were randomly assigned to use one of the three methods, they could choose to switch methods or stop using contraception at any time. High-quality research standards were achieved, note investigators; retention was 93.6% through to the final study visit, and participants used their assigned contraceptive methods for 91.9% of follow-up time.

Women who participated in the trial desired reliable contraception. The only risk factor was living in an area with high HIV prevalence. All participants received counseling, condoms, and other HIV prevention services during every study visit. Despite these measures, HIV incidence was high: 397 HIV infections occurred, or 3.81% per year.

Study investigators designed the trial to detect a 50% increase in new HIV infections for each of the three contraceptive methods compared to other methods. The study did not include a control group, as it would have been unethical to administer a placebo or no method; its design focused on the comparative risks and benefits of several contraceptive options.

Of the 397 HIV infections that occurred during the trial, 143 were recorded among women in the DMPA group, 138 were in the copper IUD group, and 116 were in the implant group. HIV incidence per year by group was 4.19%, 3.94%, and 3.31%, respectively. The trial did not find a substantial difference in HIV risk among the methods evaluated; no method showed a 50% increase in HIV risk compared to the other two.

All three study methods showed high contraceptive effectiveness, with pregnancy rates of about 1% or less per year in analyses that excluded time off method. Seven percent of women experienced complications or side effects resulting in method discontinuation.1

Push Is On for HIV Prevention

The “alarmingly high” HIV incidence among study participants spotlights the need for more aggressive efforts to prevent HIV, as well as for integration of HIV prevention, including pre-exposure prophylaxis (PrEP), into contraceptive services, says ECHO management committee member Jared Baeten, MD, PhD, professor and vice chair of the Department of Global Health at the University of Washington Schools of Medicine and Public Health.

“Our results can help contraceptive providers and policymakers deliver high-quality, integrated, rights-based care,” Baeten notes. “Even more important, the results can help women make informed choices about how to protect themselves from HIV and unintended pregnancy, but only if they have the information they need and the means to act on it.”

“The women in this trial are our sisters and daughters and mothers who were simply seeking contraception,” adds Lillian Mworeko, executive director of the International Community of Women Living with HIV/AIDS Eastern Africa and co-chair with AVAC, of the Civil Society HC-HIV Advocacy working group, an Africa-based network of women and allies working on HIV and sexual and reproductive health and rights. “It is a wake-up call to put HIV prevention onsite at every family planning clinic, including PrEP and female condoms with peer support and trained providers.”

Investigators from the New York City-based Population Council are looking at several ways to develop and expand improved contraceptive and HIV prevention methods. Scientists are researching an oral contraceptive and HIV-prevention method in a single pill, combining the two drugs now currently used in oral PrEP with a widely available combined oral contraceptive. The Population Council also is expanding contraceptive options with the newly approved Annovera, a segesterone acetate and ethinyl estradiol vaginal ring that provides an entire year of protection against unintended pregnancy while fully under a woman’s control.

What Is the Next Step?

The WHO Guideline Development Group was set to convene at the end of July 2019 to consider the most recent research on contraception and HIV risk, including the ECHO trial results. The group will determine whether any changes are needed for the WHO’s Medical Eligibility Criteria, which serve as global guidance on contraceptive use. Recommendations were scheduled to be released at the end of August 2019.

Such updated guidance may soon be reflected in the U.S. Medical Eligibility Criteria for Contraceptive Use. In 2017, the CDC revised its recommendation on DMPA by women at high risk for HIV from Category 1 (no restriction) to Category 2 (benefits outweigh theoretical or proven risks).3 The guidance called for continued access to the contraceptive shot for women at high risk for HIV, but they should be counseled about a possible, but uncertain, increased risk of acquiring HIV and how to reduce their risk.3

REFERENCES

  1. Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: A randomised, multicentre, open-label trial. Lancet 2019; doi:10.1016/S0140-6736(19)31288-7.
  2. Polis CB, Curtis KM, Hannaford PC, et al. An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women. AIDS 2016;30:2665-2683.
  3. Tepper NK, Krashin JW, Curtis KM, et al. Update to CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Revised recommendations for the use of hormonal contraception among women at high risk for HIV infection. MMWR Morb Mortal Wkly Rep 2017; 66:990-994.