Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out
Hapgood JP
Published May 2020AIDS research and human retroviruses, 36(5), 357-366
Hapgood, J. P. (2020). Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out. AIDS research and human retroviruses, 36(5), 357-366. https://doi.org/10.1089/AID.2019.0228
Hapgood JP. Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out. AIDS research and human retroviruses. 2020;36(5):357-366. doi:10.1089/AID.2019.0228
Hapgood, Janet P. "Is the Injectable Contraceptive Depo-Medroxyprogesterone Acetate (DMPA-IM) Associated with an Increased Risk for HIV Acquisition? The Jury Is Still Out." AIDS research and human retroviruses, vol. 36, no. 5, 2020, pp. 357-366.
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Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa03p74gp79
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RRM Academy Synopsis
ECHO trial leaves DMPA-IM and HIV risk open, commentary argues
A 2020 commentary reviews the ECHO trial of 7,928 girls and women and argues that the question of whether the injectable contraceptive DMPA-IM raises HIV risk remains open. Two of the trial's three method comparisons were inconclusive, and no group used no contraception. The author also examines press coverage.
Key Findings
Two of the three ECHO comparisons were inconclusive. Their confidence intervals spanned both 1.0 and 1.5, so a 50% higher risk of one method over another remained possible.
In the causal-continuous analysis, DMPA-IM versus the levonorgestrel (LNG) implant gave 1.29 (0.98–1.71), p = .06. The intention-to-treat point estimate was 23% higher risk, p = .09.
After adjustment for baseline covariates without weighting, the DMPA-IM versus LNG implant estimate was 34% with p = .029, and the confidence interval excluded 1.00.
If DMPA-IM raised HIV risk by 25% or 50% relative to no contraception, the author estimates 5,387 or 10,340 new infections in women and girls per year in South Africa.
Two earlier meta-analyses of observational studies reported a 40%–50% increased risk with DMPA-IM compared with women not using hormonal contraception: aHR 1.50 (95% CI 1.24–1.83) and aHR 1.40 (95% CI: 1.23–1.59).
Interpretation
The paper is a critical commentary on one randomized trial and reports no new trial data. The author argues that the open-label ECHO design compared three methods with each other and had no group using no contraception or only infrequent condoms, so the results address differences among those methods. Follow-up lasted 18 months. Participants were girls and women in sub-Saharan Africa, with 9 of 12 sites in South Africa. The commentary states the author's own view.
RRM Context
DMPA-IM is a suppressive medication. Restorative reproductive medicine looks for the cause of a cycle problem and works with the body. The commentary adds to evidence that safety questions about suppressive medications remain under scientific debate. It documents the WHO move of DMPA-IM to category 1 for women at high HIV risk in August 2019, a decision the author says appears based primarily on this trial.
Our editorial summary of this paper, not the article's abstract.
Abstract
Intramuscular depo-medroxyprogesterone acetate (DMPA-IM) is the most widely used hormonal contraceptive in sub-Saharan Africa. Previous meta-analyses of observational studies found a significant 40%-50% increased risk associated with DMPA-IM use, relative to no contraception or infrequent condom use. This raised substantial concerns, although these studies had important limitations. Consequently, the open-label randomized Evidence for Contraceptive Options and HIV Outcomes trial was conducted, designed primarily to detect a 50% or greater difference in HIV risk between DMPA-IM, the levonorgestrel (LNG) implant, and the copper-intrauterine device. The ECHO study, published in July 2019, concluded that there is no substantial difference in HIV risk among the methods evaluated, and that all three methods are safe and highly effective. In response, the WHO relaxed the Medical Eligibility Criteria for DMPA-IM use among women at high HIV risk in August 2019. However, two of the three comparisons in the ECHO trial could rule out neither a 50% increase nor no change in HIV risk for one contraceptive compared with another. The study had limitations and the results contained considerable uncertainty. They also did not inform on associated HIV risk for any one of the individual methods due to the absence of a control group such as no contraception or only infrequent condom use. The HIV risks associated with LNG implant and copper-IUD relative to no contraception or infrequent condom use are unknown and these cannot be seen as controls, nor did the authors claim them to be. The results will be discussed in the context of their limitations, what they add to the body of work to date on contraception and HIV acquisition, and the implications of the findings and reports thereof for future research and contraceptive choice.
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