Lauren Ralph, an epidemiologist at the University of California, San Francisco, was publicly skeptical five years ago that such a trial could be done well. But on Thursday she called it a “rigorous, well-executed study on a really complex topic.”
Noting the slight risk elevation for Depo-Provera, however, Dr. Ralph said she hoped the debate would not become so “settled” in favor of injectable hormones that work stopped on newer, even safer options for women.
In the study, over 7,800 women in South Africa, Kenya, Zambia and eSwatini — the former Swaziland — got Depo-Provera; Jadelle, an implant containing the hormone levonorgestrel; or Injeflex, a copper-infused IUD.
There was no control group of women denied contraception. That would be unethical, the authors said, since all the participants were recruited at clinics as they sought birth control. Moreover, unwanted pregnancies kill many women and infants in Africa, or lead to abortions.
For ethical reasons, as well, the women were given condoms and safe-sex advice, even though that should have reduced the odds they would get infected, the outcome that investigators were measuring.
In the trial’s final months, the women were also offered pre-exposure prophylaxis, or PrEP — a drug to prevent H.I.V. infection — as soon as it became standard treatment in their respective countries.
Over the course of the study, and despite all the precautions offered them, 397 women became infected. That alarmingly high rate — almost 4 percent a year — was even greater than other investigators had found in earlier trials of prevention methods.