No elevated HIV risk with intramuscular DMPA vs IUD, levonorgestrel
The use of intramuscular depot medroxyprogesterone acetate (DMPA-IM) did not increase a woman’s risk of acquiring HIV compared with the use of a copper intrauterine device (IUD) or a levonorgestrel implant, results of a study conducted by the ECHO* Trial Consortium show.
“Our randomized trial did not find a substantial difference in HIV risk among the contraceptive methods evaluated, and all methods were safe and highly effective at preventing pregnancy,” said study co-author Professor Jared Baeten, vice chair of the Department of Global Health, University of Washington, Washington, US.
“These results underscore the importance of continued and increased access to these three contraceptive methods, as well as expanded contraceptive choices, complemented by high-quality HIV and [sexually-transmitted infection] prevention services,” said co-author Professor Helen Rees, executive director of the Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa.
The participants were 7,829 HIV-seronegative women aged 16–35 years (median age 23 years) from 12 sites in eSwatini, Kenya, South Africa, and Zambia who were seeking contraception and had not used injectable, intrauterine, or implantable contraception in the past 6 months. They were randomized to receive injectable DMPA-IM (150 mg/mL every 3 months; n=2,609), a copper IUD (n=2,607), or a levonorgestrel implant (n=2,613) for 18 months. The 7,715 women included in the final analysis had used their assigned contraceptive method for 9,567 women-years of follow-up. They were also regularly advised to use condoms to prevent HIV and other sexually-transmitted infections.
At study onset, 18 percent of the women had Chlamydia trachomatis, 5 percent had Neisseria gonorrhoeae, and 38 percent had herpes simplex virus type 2 (HSV-2) infections.
There were 397 HIV infections that occurred over the follow-up period, at a rate of 3.81 per 100 woman-years (4.19, 3.94, and 3.31 per 100 woman-years among DMPA-IM, IUD, and levonorgestrel users, respectively). [Lancet 2019;doi:10.1016/S0140-6736(19)31288-7]
The risk of acquiring HIV infection did not significantly differ according to contraceptive method used, be it for DMPA-IM (hazard ratio [HR], 1.04, 96 percent confidence interval [CI], 0.82–1.33; p=0.72 compared with IUD and HR, 1.23, 96 percent CI, 0.95–1.59; p=0.097 compared with levonorgestrel) or IUD (HR, 1.18, 96 percent CI, 0.91–1.53; p=0.19 compared with levonorgestrel).
Age and HSV-2 status did not significantly affect the association between contraception method and risk of HIV infection.
Of the 12 deaths that occurred during the study, six and five were DMPA-IM and IUD users, respectively, and one a levonorgestrel user. Serious adverse events (AEs) occurred at a comparable rate between DMPA-IM, IUD, and levonorgestrel users (2, 4, and 3 percent, respectively). Of these, 22 and 13 percent that occurred in IUD and levonorgestrel users, respectively, and none among DMPA-IM users, were deemed contraceptive method-related. AE-related discontinuations occurred significantly less frequently in DMPA-IM users than IUD (4 percent vs 8 percent) or levonorgestrel users (9 percent; p<0.0001 for both comparisons).
A total of 255 pregnancies occurred – 24, 45, and 31 percent of which were in DMPA-IM, IUD, and levonorgestrel users, respectively – with 71 percent occurring after discontinuation of contraception. Pregnancy occurred less frequently in DMPA-IM and levonorgestrel users than IUD users (p=0.027 and p=0.042, respectively).
This trial was conducted to clarify if an association existed between DMPA-IM use and an elevated risk of HIV infection, following two previous meta-analyses that suggested a link. [AIDS 2016;30:2665-2683; PLoS Med 2015;12:e1001778] However, results of the individual studies included in the analyses had limitations including observational study design and contradictory findings.
Identifying a risk of HIV associated with DMPA-IM use is particularly crucial in countries where DMPA-IM is widely used and where there is a high HIV prevalence, said co-author Dr Nelly Mugo from the Kenya Medical Research Institute, Nairobi, Kenya.
“The results of this study are reassuring, but 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,” said Rees.
“[These results] highlight the need for more aggressive efforts to prevent HIV and for integration of HIV prevention, including pre-exposure prophylaxis (PrEP), into contraceptive services,” added Baeten. “Our results can help contraceptive providers and policy makers deliver high-quality, integrated, rights-based care … [and] 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 authors pointed out that the findings only pertain to the three contraceptive methods used in the trial and as such, cannot be generalized to other contraceptive methods. Furthermore, the study was only powered to detect a 50 percent increase in HIV incidence for each contraceptive method over the other and not an increase of less than 30 percent.
“[F]or individual women at very high HIV risk, we acknowledge that even a relatively small effect might be important in contraceptive and HIV prevention decision making,” they said.