A landmark study has ended 30 years of anxiety that hormonal contraceptive injections may increase women’s chances of infection from HIV.

But the study found a dramatically higher rate of HIV infection among women in southern Africa than was expected, which one leading campaigning organisation said signified a public health crisis”.

In many African countries with high HIV rates, women predominantly use DMPA-IM, known as Depo-provera – three-monthly injections that allow them to keep their use of contraception secret from their partner.

For three decades there have been concerns and in 2011 the Lancet published evidence that women using the progestogen-only injections to avoid pregnancy were twice as likely to become HIV-positive.

In 2012 the World Health Organization advised couples to use condoms as well, which is not always negotiable in some communities. In sub-Saharan Africa, nearly 60% of all new infections occur in women. There were calls for new methods of contraception that would also prevent HIV and be controlled by women themselves.

Further research published in the journal Lancet Infectious Diseases in 2015 found that women using the injections for contraception were 40% more likely to get HIV. However, the authors said the dangers had to be balanced against a woman’s risk of an unwanted pregnancy, which could also jeopardise her life. The WHO said in 2017 that women should be advised of the risk.

The new study, called Echo (Evidence for Contraceptive Options and HIV Outcomes), published in the Lancet, was designed to put an end to the controversy. It compared the HIV infection rates among women using hormonal injections with those using an IUD (intrauterine device or coil) or an implant. It involved more than 7,800 women in Eswatini, Kenya, South Africa and Zambia.

“Our randomised 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 one of the study’s co-authors, Prof Jared Baeten, of the University of Washington, USA.

The WHO will now review its guidance and is likely to say that women should no longer be concerned about the injectables or have to choose between the possibility of pregnancy and the fear of HIV infection.

But there is alarm at the high rate of HIV infection among the women in the trial – which was 3.8%, and worse in women under 25. The infection rate was higher than the “substantial risk” rate of 3% that the WHO says should trigger the use of PrEP (pre-exposure prophylaxis), a daily antiviral drug which protects against infection.

“The study highlights the need to step up HIV prevention efforts in these high-burden countries, particularly for young women,” said Dr Rachel Baggaley, of the WHO’s HIV and Hepatitis department. “These should include providing HIV testing and a range of HIV prevention choices within contraceptive service programmes.”

Prof Helen Rees, of the University of Witwatersrand in Johannesburg, South Africa, a member of the study’s management committee, said: “The results on this question are reassuring but our findings are also sobering because they confirm unacceptably high HIV incidence among young African women.”

AVAC, a global HIV advocacy organisation, said there was good news and bad news. The trial had shown that the injectables were safe. On the other hand, it “delivered a sobering reminder that women and girls in east and southern Africa are still at very high risk of HIV infection. An overall HIV infection rate of almost 4% in the study points to a public health crisis for women in the region,” said Mitchell Warren, AVAC’s executive director.

The trial participants were not considered to be at high risk. “The women in this trial are our sisters and daughters and mothers who were simply seeking contraception,” said Lillian Mworeko, executive director of the International Community of Women Living with HIV/AIDS Eastern Africa. “It is a wake-up call to put HIV prevention onsite at every family planning clinic, including PrEP and female condoms with peer support and trained providers.”

Yvette Raphael, a member of the global community advisory group for the Echo study, said women needed more options for contraception combined with HIV protection. “Regardless of the data from the Echo trial, the limited choice of contraceptives that women have is not OK. We hope that this result will prompt action and put women first. Women want more options,” she said.