After years of uncertainty, a landmark study published June 13 in The Lancet finds that hormonal contraception does not increase cisgender women’s risk of acquiring HIV.
The news comes as a welcome relief for public health experts and advocates who worried about the possible link between hormones used in birth control and HIV acquisition risk - a link that was first established in animal studies and later seen in observational research in humans.
The Evidence for Contraceptive Options and HIV Outcomes (ECHO) was a large, randomized study that evaluated three different types of long acting contraception - non-hormonal intrauterine device (copper IUD), injectable hormonal contraceptive (DMPA-IM) and implanted hormonal contraceptive (LNG implant).
ECHO did not find a meaningful difference in the rate of HIV infection among women using the various methods. This is particularly notable for DMPA-IM, which was the subject of greatest concern and is also one of the most popular contraceptive methods in Africa.
“After decades of uncertainty, we finally have high-quality scientific evidence about the potential relationship between three different types of contraceptives and the risk of HIV from a rigorous randomised clinical trial,” said Wits RHI Executive Director Helen Rees, MD, MA, MRGCP a member of the five-person ECHOManagement Committee (MC) that leads the ECHO Study, according to a press release.
Although the results have put worries about DMPA-IM to rest, the HC-HIV Civil Society Working Group, an Africa-based group advocating for reproductive rights, cautioned that “the ECHO results are not ‘good news’. DMPA-IM currently dominates women’s contraceptive programs in East and Southern Africa, with the advocacy group noting that the ECHO results should reinforce the importance of giving women a range of contraceptive options.
Beyond its primary objective, the ECHO study also served as an important reminder of the high rate of HIV infection among African women, with about 5% of the women acquiring HIV throughout the course of the study.
“Our findings are also sobering, because they confirm unacceptably high HIV incidence among young African women irrespective of which contraceptive method they were assigned to,’ added Rees, according the release.
Results were presented June 13 at the South African AIDS Conference in Durban, South Africa, and published simultaneously in The Lancet. The ECHO study represents an extraordinary level of cooperation between more than 20 groups, including FHI 360, the University of Washington, Wits Reproductive Health and HIV Institute (Wits RHI) and the World Health Organization (WHO).
“Women, mostly, get HIV and get pregnant through sex -- yet we treat this as though these are separate things,” said Beth Schlachter, Executive Director of Family Planning 2020, a global consortium that helped orchestrate the landmark study, who spoke during an AVAC webinar immediately following the study’s publication.
By examining both pregnancy rates and HIV rates in tandem, the ECHO study offers meaningful insights that can be used to inform public health policies.
ECHO launched in December 2015, and enrolled 7,829 sexually active young women in Eswatini, Kenya, South Africa, and Zambia over the next three years. All the women expressed interest in long-acting contraception, and were randomly assigned to receive a copper IUD, DMPA-IM or the LNG implant.
Although all women were given the option of switching or stopping contraception any time they liked, the study had an extraordinarily high level of ongoing participation, with 99% of the women completing at least one post-randomization HIV test, and 93.6% remaining engaged throughout the study. On average, women used their contraception method for 92% of the time they were enrolled in the study.
ECHO was carefully designed so that it would be statistically meaningful. From the outset, the study was designed with an 80% power to detect a 50% increase in HIV risk. Authors set a high bar because they felt it was important to be able to arm policy makers with ironclad-data once the study was completed.
There was no placebo arm comprised of women not using any form of contraception. Instead, copper IUD served as a comparison to the two hormonal methods - the shot and the implant. On average, women enrolled in the study were 23 years old. More than 80% were not married, and had already been pregnant at least once before. Condom use was low (about 50% reported at last sex act), and the number of sex partners was also low, with only 7% reporting more than one sex partner in the prior 3 months.
None of the women had HIV upon enrollment, but the rate of other STIs was high, with an 18% rate of chlamydia, 5% rate of gonorrhea, and 38% rate of herpes.
Ultimately, 2,607 women were randomized to receive the copper IUD, 2,609 DMPA-IM and 2,613 the LNG implant. At the end of the study, there were 138 HIV infections among the women using a copper IUD, 143 among women who received the DMPA-IM shot and 116 among the women who received the LNG implant.
That translates to an HIV incidence rate of 3.94, 4.19 and 3.31, respectively, per 100 woman-years. Although those results may seem disparate, the study was powered in such a way that when compared against one another, DMPA-IM and LNG implants were no more likely than the copper IUD to be associated with a greater HIV infection risk.
Specifically, DMPA-IM compared to copper IUD had a hazard ratio of 1.04 and p value of 0.72, DMPA-IM compared to LNG implant had a hazard ratio of 1.23 and a p value of 0.097 and the copper IUD compared to the LNG implant had a hazard ratio of 1.18 with a p value of 0.19. All three comparisons had a 96% confidence interval.
Researchers also looked at specific subgroups, such as women under the age of 25, and women who had herpes infection, to determine if risk differed in these groups. Overall, however, they found that the HIV infection risk among these subgroups were also consistent across contraception methods.
Notably, 397 out of 7,829 women acquired HIV during the study for an overall HIV infection rate of 3.81% per year (95% CI 3.45-4.21). This finding is significant because all of the women who enrolled in the study received condoms and HIV prevention educational materials. In addition, when PrEP became available in 2017, they were offered an HIV prevention pill as well.
Speaking during a webinar on the study hosted by AVAC, Schlachter thanked the “many women who put their bodies on the line” to participate in the ECHO study.
“What is clear from this trial,” she said, “is that women want to be able to choose.”