No Substantial Difference in HIV Risk Using Injectable, Intrauterine, or Implantable Contraceptives

When comparing hormonal contraceptive methods, particularly intramuscular (IM) depot medroxyprogesterone acetate with a copper intrauterine device (IUD) and a levonorgestrel implant, there was no substantial difference in HIV risk among African women living in areas of high HIV incidence, according to results from a study recently published in the Lancet.¹

In this randomized, multicenter, open-label trial (Evidence for Contraceptive Options and HIV Outcomes [ECHO]; ClinicalTrials.gov identifier: NCT02550067) at 12 research sites in eSwatini, Kenya, South Africa, and Zambia, researchers randomly assigned women aged 16 to 35 years (median age, 23 years) in a 1:1:1 ratio to receive an IM depot medroxyprogesterone acetate every 3 months (injection of 150 mg/mL), a copper IUD, or a levonorgestrel implant with random block sizes between 15 and 30, stratified by site. Because prior studies^2,3 have suggested that use of IM depot medroxyprogesterone acetate may increase a woman’s susceptibility to HIV, the primary objective of this study was to compare HIV incidence among women using these 3 contraceptive methods.

The primary outcome was assessed in a modified intention-to-treat population, which included only women who tested negative for HIV at enrollment and those who contributed an HIV test at follow-up every 3 months for 18 months. Across the 3 groups throughout the trial, counseling messages related to HIV risk, including pre-exposure prophylaxis and condom use, were designed and implemented consistently.

Of the 7829 women enrolled, 2556 women in the IM depot medroxyprogesterone acetate group, 2571 women in the copper IUD group, and 2588 women in the levonorgestrel implant group were included in the modified intention-to-treat analysis. Researchers observed 397 incident HIV infections with a high overall HIV incidence (3.81 per 100 woman-years; 95% CI, 3.45-4.21).

In the modified intention-to-treat analyses, the hazard ratios for HIV acquisition were 1.04 (96% CI, 0.82-1.33; P =.72) for IM depot medroxyprogesterone acetate vs copper IUD, 1.23 (96% CI, 0.95-1.59; P =.097) for IM depot medroxyprogesterone acetate vs levonorgestrel implant, and 1.18 (96% CI, 0.91-1.53; P =.19) for copper IUD vs levonorgestrel implant. HIV incidence was high for all 3 groups, with no substantial differences across groups. Moreover, results from the continuous use and causal analysis generated similar results.

All 3 contraceptive methods were well tolerated: fewer than 4% of participants in any group reported a serious adverse event, and fewer than 9% reported adverse events resulting in method discontinuation. In addition, all 3 contraceptive methods were highly effective against pregnancy. In the continuous use analysis, pregnancy rate was approximately 1% or less per year.

A key limitation of this study was the inability to generalize results to other contraceptive methods such as etonogestrel implant, subcutaneously administered depot medroxyprogesterone acetate, oral contraceptive pills, injectable norethisterone enanthate, combined progestin and estrogen injectable contraceptives, or hormonal IUDs.

In an editorial commentary, Noguchi and Simelela note that there are many factors driving high rates of HIV acquisition in young women, but there are good reasons to believe that contraception is not one of them.

“Decision makers need to listen to the voices of women and girls — who continue to suffer and die not solely as a result of their unconscionable lack of access to high-quality contraceptive and HIV-related care but also to primary care, cancer prevention, mental health, safe abortion, violence prevention, and maternal health services,” stated Noguchi and Simelela. “Therein lies the message we need to hear and amplify as we listen to results of ECHO,” they concluded.

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 [published online June 13, 2019]. Lancet. doi:10.1016/S0140-6736(19)31288-7
2. Morrison CS, Chen PL, Kwok C, et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med. 2015;12(1):e1001778.
3. 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(17):2665-2683.
4. Noguchi LM, Simelela PN. How should we listen to ECHO? [published online June 13, 2019]. Lancet. doi:10.1016/S0140-6736(19)31387-X