It’s been a 30-year wait marked with red flags, speculation and worry but today a new study has answered the question on whether a commonly used hormonal contraceptive causes increases risk among women for the acquisition of HIV.
The short answer – it doesn’t.
The pivotal clinical trial known as the Evidence for Contraceptive Options and HIV Outcomes (Echo) Study was designed to compare the HIV incidence among women using three contraceptive methods.
These were: the progestin-only depot-medroxyprogesterone acetate, given via injection (DMPA-IM) or commonly known as Depo-Provera; a non-hormonal copper intrauterine device (copper IUD); and a progestin-based implant containing the hormone levonorgestrel (LNG implant).
It’s objective? To get high-quality evidence to help women at high risk of HIV infection make informed choices about their contraceptive choices.
The study, which enrolled 7 829 African women in December 2015 and ran until October last year, found that there was “no substantive difference in HIV risk” among the contraceptive methods used.
Although these were all highly effective contraceptive options for women, the risk for HIV was relatively similar for all three methods because at least 397 women in the trial contracted HIV despite being offered a comprehensive package of HIV prevention package.
It also means that there is no need to remove Depo-Provera from the contraceptive method choices women currently have.
The results of the trial were announced this afternoon – by a research consortium led by FHI 360 (a non-profit human development organisation), the University of Washington, Wits Reproductive Health and HIV Institute (Wits RHI) and the World Health Organization (WHO) – at the South African AIDS Conference in Durban, and published simultaneously in The Lancet.
At least nine of the 12 research sites were in South Africa (the others were in Kenya, Zambia and Swaziland) and all of them enrolled women aged between 16 and 35.
“Contraception is extremely important for the health of women and for the health of children and communities and families. Modern contraception is currently used by more than 700 million women worldwide, including 58 million African women,” Professor Helen Rees, Wits RHI executive and member of the five-person Echo management committee that led the study said.
Rees, who was speaking at a media briefing held ahead of the release of the results, added that they had been “extremely worried” about the African region because there were about 600 000 new HIV infections a year among African women – the majority of which were in South Africa.
She continued: “There were some flags of concern as far back as 30 years ago that there might be an increase as far as the acquisition of HIV, associated with certain contraceptives, particularly Depo-Provera. And to try and answer this question there have been numerous studies both epidemiological and observational, as well as cohort and laboratory studies trying to answer this question.
But all of them have had some sort of inherent bias and lab studies can’t predict what happens in the real world of clinical use. So because of this it was felt that further research needed to be done.”
A meta-analysis (examination of data from other studies) undertaken four years ago indicated that there might be an increased risk of HIV from using Depo-Provera by as much as between 40% and 50%.
But there was very little data on the other contraceptive methods regarding HIV acquisition.
And so informed the basis of the trial.
According to Dr Timothy Mastro, chief science officer at FHI 360, the three methods were chosen because:
• Previous studies suggested depo-provera might increase HIV susceptibility and is a commonly used contraceptive in many settings, including Africa; and
• The copper IUD was included as a highly effective non-hormonal comparator and the implant (hormonal) was included because use of long acting contraceptives was rapidly increasing in many settings.
The trial was designed to detect a 50% increase in new HIV infections for each of the three contraceptive methods compared with each other method.
Of the enrolled 7829 women – 2609 were assigned to Depo-Provera, 2 607 the implant, and 2613 the copper IUD.
They received comprehensive HIV prevention package, including HIV risk reduction counselling, testing and treatment for sexually transmitted infections, condoms and a Pre-exposure prophylaxis (PrEP).
The rate of HIV infection overall was 3.81% a year – with 397 of the enrolled participants acquiring HIV during the study. The infections could be further broken down by contraceptive method to: 143 women who were assigned to Depo-Provera, 138 infections for those on the copper IUD, and 116 infections in women on the implant.
The trial did not find a substantial difference in HIV risk among the methods evaluated: no method showed a 50% increase in HIV risk compared to the other two.
However, a high number of the women still contracted HIV despite being given access to a comprehensive package of HIV prevention services and PrEP, Rees said.
“Unfortunately one of the things we’ve learnt through doing many years of HIV prevention studies is that even if we do optimise what we know about prevention, the truth of the matter is that many women are living in contexts with tools that are limited in their ability to be used. It is not possible to have 100% perfect use of what we offer for many women, whether that’s a male or female condom.”
And even in terms of PrEP, not all women will want to use it and even those who take it may have difficulty using it continuously.
The study members said the results supported women continuing on all these three methods of contraception.
However, Dr Jared Baeten, professor and vice chair of the department of global health at the University of Washington Schools of Medicine added: “The alarmingly high HIV incidence among study participants highlights the need for more aggressive efforts to prevent HIV and for integration of HIV prevention, including pre-exposure prophylaxis into contraceptive services.”