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

Abstract

Summary Background Observational and laboratory studies suggest that some hormonal contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM), might increase women's susceptibility to HIV acquisition. We aimed to compare DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant among African women seeking effective contraception and living in areas of high HIV incidence. Methods We did a randomised, multicentre, open-label trial across 12 research sites in eSwatini, Kenya, South Africa, and Zambia. We included HIV-seronegative women aged 16–35 years who were seeking effective contraception, had no medical contraindications to the trial contraceptive methods, agreed to use the assigned method for 18 months, and reported not using injectable, intrauterine, or implantable contraception for the previous 6 months. Participants were randomly assigned (1:1:1) to receive an injection of 150 mg/mL DMPA-IM every 3 months, a copper IUD, or a LNG implant with random block sizes between 15 and 30, stratified by site. Participants were assigned using an online randomisation system, which was accessed for each randomisation by study staff at each site. The primary endpoint was incident HIV infection in the modified intention-to-treat population, including all randomised participants who were HIV negative at enrolment and who contributed at least one HIV test. The primary safety endpoint was any serious adverse event or any adverse event resulting in method discontinuation, until the trial exit visit at 18 months and was assessed in all enrolled and randomly assigned women. This study is registered with ClinicalTrials.gov , number NCT02550067 . Findings Between Dec 14, 2015, and Sept 12, 2017, 7830 women were enrolled and 7829 were randomly assigned to the DMPA-IM group (n=2609), the copper IUD group (n=2607), or the LNG implant group (n=2613). 7715 (99%) participants were included in the modified intention-to-treat population (2556 in the DMPA-IM group, 2571 in the copper IUD group, and 2588 in the LNG implant group), and women used their assigned method for 9567 (92%) of 10 409 woman-years of follow-up time. 397 HIV infections occurred (incidence 3·81 per 100 woman-years [95% CI 3·45–4·21]): 143 (36%; 4·19 per 100 woman-years [3·54–4·94]) in the DMPA-IM group, 138 (35%: 3·94 per 100 woman-years [3·31–4·66]) in the copper IUD group, and 116 (29%; 3·31 per 100 woman-years [2·74–3·98]) in the LNG implant group. In the modified intention-to-treat analysis, the hazard ratios for HIV acquisition were 1·04 (96% CI 0·82–1·33, p=0·72) for DMPA-IM compared with copper IUD, 1·23 (0·95–1·59, p=0·097) for DMPA-IM compared with LNG implant, and 1·18 (0·91–1·53, p=0·19) for copper IUD compared with LNG implant. 12 women died during the study: six in the DMPA-IM group, five in the copper IUD group, and one in the LNG implant group. Serious adverse...

Impact of etonogestrel implant use on T-cell and cytokine profiles in the female genital tract and blood

“…Notably, these findings have not been consistently demonstrated by all studies, and all the studies were observational thus prone to potential confounding. Further, the findings have been challenged by the results from the Evidence for Contraceptive Options and HIV outcomes (ECHO) study [4], a large randomized trial that found no significant increase in HIV risk among users of DMPA compared to copper intrauterine device and levonorgestrel implant users. While these data are reassuring, gaps remain in our understanding of the relative HIV risk with contraceptive use compared to non-use and the impact of other progestin-containing contraceptive methods.…”

Epidemiological impact and cost‐effectiveness of providing long‐acting pre‐exposure prophylaxis to injectable contraceptive users for HIV prevention in South Africa: a modelling study

“…An area that has shown success in long‐acting drug delivery modalities are injectable contraceptives which are used by 25% of South African women aged 15 to 49 years . While some observational studies suggested progesterone‐based injectables, particularly depot medroxyprogesterone acetate (DMPA), might increase the risk of HIV infection , a recent randomized controlled study did not find an increased risk for HIV for women using DMPA as compared to women using other contraceptive methods . However, women using injectable contraceptives might still be an interesting target population for injectable forms of long‐acting PrEP.…”

Counseling on injectable contraception and HIV risk: Evaluation of a pilot intervention in Tanzania

“…The study was designed to address whether there is an increased risk of HIV acquisition when comparing women using DMPA with Cu-IUD, DMPA with levonorgestrel implant, and Cu-IUD with levonorgesterel implant. The results from the trial were published in mid-2019, and show that there is not an increased risk of HIV incidence among users of DMPA as compared to users of Cu-IUD or the implant [2]. The findings support the continued use of these methods in areas of high incidence of HIV.…”

“…The findings support the continued use of these methods in areas of high incidence of HIV. However, the overall HIV incidence in the study population was 3.8 per 100 woman-years, which is "alarmingly high", and signals a need for strengthened family planning (FP)/HIV programming [2].…”