Growing concern over HIV risk from Depo Provera injection
The evidence that one of South Africa's most commonly used contraceptives‚ the Depo-Provera injection‚ increases the risk of contracting HIV is "accumulating".
Yet Pfizer‚ the maker of the drug‚ continues to deny there may a problem.
About half of women accessing government contraception have at least once used the long-acting injection‚ according to a 2017 study in the South African Medical Journal.
The injection - needed once every three months - contains the synthetic hormone medroxyprogesterone acetate (MPA)
The drug could make it up to 40% easier to contract HIV‚ a 2016 review‚ of all the studies on the hormone and risk of HIV acquisition in women concluded.
(Note: The contraception injection given every two months‚ known as NET-EN - does not show a risk of being able to contract HIV.))
But the evidence on MPA in human trials is not conclusive‚ due to the quality and type of studies.
The World Health Organisation's explains it is not clear if the increased risk could be due to "methodological issues with the evidence or a real biological effect".
This is where the University of Cape Town molecular endocrinologist Janet Hapgood and two international scientists come in.
The trio have just published a review of all the animal and laboratory studies that reveal how the synthetic hormone could affect the body's immune system and a molecular and cellular level and increase the risk of acquiring HIV.
While clinical studies observing HIV risk in women using this contraceptive are inconclusive‚ the laboratory data Hapgood has reviewed is not.
"I have looked at it from a scientist's point of view and from that view depot medroxyprogesterone acetate is a problem. I wouldn't use it based on my scientific opinion. For me it would not be worth the risk."
"The evidence [for risk] is accumulating‚" said Hapgood‚ who has spent 20-years looking at what synthetic hormones do to human cells from women's bodies.
The study is published in the journal Endocrine Reviews.
"The bottom line of our journal article is if you look at all the [biological] evidence‚ it supports the finding that medroxyprogesterone acetate increases the risk of contracting HIV."
The review shows the synthetic hormone MPA acts as an immune suppressant‚ making the immune system weaker.
Hapgood says: "The immune system‚ in general does quite a good job of defending against HIV in the genital tract."
The immune system's response means that many unprotected sex acts with an HIV-positive person won't actually lead to an HIV infection. The immune system can sometimes prevent viruses from infecting the body‚ explained Hapgood.
Weakening the immune system makes contracting HIV easier.
Scientists have long known the synthetic hormone MPA increases an animal's chances of acquiring viruses. Some HIV researchers have given it to chimpanzees to increase their chance of contracting Simian HIV. Doctors also know using this hormone at high concentrations‚ ten times that of what is used in contraception‚ can weaken the immune system‚ when used as part of a cancer patient's treatment.
The new review asks if much smaller concentrations of MPA‚ as in the case of contraceptives‚ still suppresses the immune system.
It does‚ explained Hapgood. "The hormone may also make it easier for the virus to travel into the body through the cells lining the genital tract‚" she said.
But what health experts should do about the contraceptive's HIV link is complicated.
"There is a lot at stake‚" explains Hapgood.
The World Health Organisation has had experts meeting regularly on the issue in Geneva‚ since at least 2012.
The difficulty is not just with the quality of human evidence‚ but the problem is the injection is the most popular form of contraception in Sub -Saharan Africa.
It is easy to take every three months without the knowledge of male partners‚ who may not approve of birth control.
It reduces the frequency poor women need to pay to travel to a clinic.
"If word gets out that it could be dangerous‚ people could stop contraception all together‚" said Hapgood.
The World Health Organisation explains it is too risky to reduce contraception options in places where the Depo Provera injection is one of the only widely available and cost effective contraceptives---especially in countries with a high maternal mortality - and many unwanted pregnancies.
Hapgood's review shows the injection given every two months- known as NET-EN does not increase risk of HIV - suggesting it is an alternative.
"Childbirth is also dangerous‚" Executive Director of the Wits Reproductive Health and HIV Institute‚ Professor Helen Rees had told The Times newspaper previously.
The World Health Organisation suggests telling women there may be an increased risk of HIV acquisition... when offering the three-monthly injection as contraception.
Four years ago‚ the South African health department started offering more alternatives to women... such as contraceptive implants‚ which contain a different synthetic hormone and can stay under the skin for three years.
But the "uptake [of the implant] has declined precipitously‚" according to Rees's October study published in the SA Medical Journal.
To get a conclusive and final answer as to whether the Depo Provera injection increases the risk of contracting HIV more than two other methods‚ Rees is in charge of a randomised controlled trial named the ECHO trial. The jab (Depo-Provera) and two other forms of contraception has been made available to 7200 HIV-negative women from Zimbabwe‚ Kenya and South Africa.
Some women are being offered the Depo-Provera injection‚ others the implant and others the intrauterine device and researchers will watch to see if HIV infection rates are higher in a particular group. Results are expected in 2019.
Pfizer has long denied there is enough evidence to show their injectable contraceptive increases the risk of HIV.
It stated: "Depot medroxyprogesterone acetate (DMPA)‚ a long-acting reversible contraceptive‚ has been available as an important contraception option to women for more than 40 years. Numerous studies have contributed to our understanding of the safe and effective use of this medicine. So far‚ there has been no scientific evidence of a causal relationship between DMPA and the acquisition of HIV."
Pfizer said it was awaiting the results of the ECHO trial.