25 years of uncertainty over for depo-provera users

Paidamoyo Chipunza Senior Health Reporter
For over 20 years, contraceptives, in particular depo-provera, an injectable progesterone-based hormonal contraceptive has been said to increase the risk of HIV acquisition and transmission for women who use it.

The debate on depo-provera increasing the risk of HIV acquisition started in 1996 when scientists discovered that monkeys injected with high concentration levels of depo-provera also known as DMPA by scientists had their biological make-up weakening, thereby allowing easy penetration of SIV, an equivalent of HIV in humans, into their system.

This raised concerns for scientists, that if such weakening was happening in monkeys humanised to mimic a normal human being’s system what could then be happening to women who use this contraception on a daily basis regardless of the concentration levels.

Since then, several studies were conducted to answer different research questions.

However, none had been conducted to specifically respond to the question on whether depo-provera indeed increased women’s risk to acquiring HIV because of ethical issues, which include further exposing women in the study to HIV acquisition, should the contraceptive indeed increase the risk of females getting HIV.

However, despite existence of studies alluding to depo-provera’s link with increased risk of getting HIV, policy makers could not make any pronunciations regarding its ban or continued use, because again these studies were not specifically looking at the link between the two.

A research scientist with the Centre for Aids Programme in South Africa (CAPRISA) Dr Sinaye Ngcapu said current studies have several limitations that prevents direct application of results into clinical practice.

“Results are from secondary analysis and prone to bias. DMPA users might have more frequent sexual intercourses. DMPA recipients might be less likely to use condoms, said Dr Ngcapu.

Because of such uncertainty in the data, a specific study to answer this research question became of paramount importance.

However, such a study had ethical issues, one of which is harm. Harm in the sense that if indeed depo-provera increased chances of women acquiring HIV, conducting such a trial would mean sacrificing participating women to acquiring HIV.

Hence for over 20 years, no study designed to respond to the link between depo-provera and HIV had been conducted.

In fact, over the years, WHO has been carefully making recommendations on the use of depo-provera depending on available evidence.

Since no study had shown this relationship, in 2014, the WHO guidelines permitted use of all hormonal contraceptives, but with a disclaimer that progestogen-only injectables, which include depo-provera may or may not increase their risk of HIV acquisition.

The 2014 guidelines further encouraged HIV preventive measures, including male and female condoms in women at high risk of HIV infection.

In 2017, WHO released revised guidelines on the use of contraceptives from which it stated that the advantages of using the contraceptives in question generally outweighed the “possible, but unproven”, increased risk of HIV acquisition.

It was until 2015 when scientists and funders took the bold step to answer the research question linking depo-provera to increased HIV acquisition.

A research consortium led by FHI 360,  the University of Washington, Wits Reproductive Health and HIV Institute (Wits RHI) and the World Health Organisation (WHO) embarked on this courageous trial, whose objectives were specifically to compare HIV acquisition between three different methods of contraceptives, which are depo-provera, a non-hormonal copper intrauterine device (copper IUD) and a progestin-based implant containing the hormone levonorgestrel (LNG implants) also known as jadelle all methods of which are commonly used by Zimbabwean women.

A total of 7 829 women from selected sites in South Africa, Zambia, Kenya and Eswatini were selected to take part in the trial code named: Evidence for Contraceptive Options and HIV Outcomes (ECHO).

To address the risk of deliberately exposing participants to HIV, all women in the study were given pre-exposure prophylaxis (Prep) throughout the study duration.

The study findings showed no statistical differences in HIV acquisition between women taking either depo-provera, jadelle or IUDs.

In fact, professor and vice chairman of the department of global health at the University of Washington who was also in the management committee, Dr Jared Baeten said instead, there was high HIV incidences among young African women irrespective of which contraceptive method one was using.

Of the 7 829 women who participated in the trial, 397 acquired HIV.

Of these, 143 were taking depo-provera, 188 were on IUDs while 116 were on implants.

“The trial did not therefore find a substantial difference in HIV risk among the methods evaluated in the study. No method showed a 50 percent increase in HIV risk compared to the other two, “ said Dr Baeten.

These results put to an end more than 25 years of uncertainty on the link between depo-provera and HIV and AIDS, bringing relief to an estimated 2,2 million Zimbabwean women using modern contraceptives.

Reassuring as the results maybe regarding the link to HIV acquisition and one’s choice of family planning, the ECHO results, however, brings with them a “sobering” revelation at least according to scientists, that is the number of women who acquired HIV during the course of the study.

“Our results strongly emphasise the need for more aggressive HIV and Sexually Transmitted Infections prevention and management efforts for African women, including pre-exposure prophylaxis and HIV prevention integrated with contraceptive services,” said WHO’s coordinator in the department of reproductive health, Dr James Kiarie.

How these women got infected when they were also on Prep, a scientifically proven method for HIV prevention boggles the mind, leaving room for assuming that some women might not have been religiously taking their Prep.

Overall, HIV transmission rates among participating women were at about 3,8 percent.

Analysing, the data from ECHO, a global advocacy for HIV prevention organisation-AVAC’s executive director Mr Mitchell Warren said previously, HIV prevention trials have often shown very high rates of HIV infection among participants because of the eligibility criteria used to recruit participants for those trials, which include characteristics that are associated with HIV risk, such as transactional sex, history of sexually transmitted infections or self-reported high-risk behaviours.

However, in the ECHO study, the only sexual behavioural eligibility criterion was being sexually active.

Mr Warren said these results therefore emphasised the need for women to urgently access expanded access to the full range of proven contraceptives and HIV prevention options, which include female condoms and daily oral Prep.

“We need to accelerate the development of and access to additional women-controlled HIV prevention options like the monthly dapivirine vaginal ring (currently pending regulatory approvals), and other long-acting methods, including vaccines.

“At the same time, ECHO provides added urgency to the development of methods that combine HIV prevention and contraception,” said Mr Warren.

Many women from Southern Africa face the double tragedy of high HIV prevalence and high maternal and infant mortality from unintended pregnancies.

An estimated 35 million women world-wide rely on depo-provera.

In Zimbabwe, according to statistics from the Ministry of Health and Child Care, from the estimated 2,2 million women who use modern contraceptives, 15 percent use depo-provera.

The others use the pill (57 percent), implants (17 percent) and condoms nine percent and in men, vasectomy is at 1 percent. Wider choices of family planning remain critical in reducing maternal and infant mortality rates from unintended pregnancies.

News that depo-provera does not increase one’s risk of acquiring HIV is therefore a relief and a step in the right direction as it gives women a wide range of scientifically proven safe and effective choices of family planning.

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