Stocks of the new treatment are already on the shelves of some clinics — but lingering concerns over a possible low risk of birth defects associated with this new antiretroviral have stalled the country’s switch to better medication for a second time.
The national health department has been forced to postpone a nationwide rollout of the latest blockbuster HIV treatment amid persistent concerns about what may be a low risk of birth defects linked to the drug’s use. This is despite the World Health Organisation (WHO) greenlighting the drug for use globally in July.
The medication, known as dolutegravir, was set to be introduced in September as part of a new three-in-one pill that would combine the relatively new antiretroviral (ARV) with two more commonly used ARVs, tenofovir and emtricitabine.
Most South Africans on HIV treatment already use these two drugs alongside a third called efavirenz. But a 2019 research review by the WHO found that dolutegravir was better than efavirenz at dropping the level of HIV in people’s blood down to very low levels — also known as being virally suppressed. It was also more forgiving of skipped doses, reducing patients’ risk of developing drug resistance.
People who are virally suppressed cannot transmit HIV, decades of research has shown. It also has fewer side effects and can be taken without food.
The WHO’s decision to recommend the drug for use globally was informed in part by South African research. Earlier this year, a study conducted among more than 1000 patients in Hillbrow by the Wits Reproductive Health and HIV Institute’s (WRHI) Ezintsha clinic found that patients on standard treatment did just as well when dolutegravir was substituted for efavirenz. The research was published in August in The New Journal of Medicine. But it also found that participants on dolutegravir were more likely to pick up weight than those on other drugs — about 5 kgs after a year.
Scientists remain uncertain about the potentially small risk of birth defects
There are also still lingering concerns about what could be a very small risk of serious birth defects, called neural tubal defects, linked to conceiving while on the drug. The condition affects the brain, spine or spinal cord. Research presented in July at the International AIDS Conference on HIV Science in Mexico City, found that three such defects per 1,000 deliveries among women in Botswana, who were on the drug when they conceived, compared to about one such deformity per 1,000 births among women taking other ARVs.
But similar studies among about 1500 Brazilian women on ARVs — a quarter of whom fell pregnant while on dolutegravir — found no birth defects. Scientists are continuing to monitor the phenomenon around the world. Meanwhile, women living with HIV globally have continued to demand access to the drug.
In South Africa, however, concerns around this prompted the National Health Council’s decision to delay dolutegravir’s rollout. At an August meeting, the body — made up of the national and deputy health ministers, as well as MECs and heads of departments, requested more information about the possible risk of birth defects and weight gain. The group also wanted more details about cost-benefit analyses done regarding the drug. One such study by Wits University’s Health Economics and Epidemiology Research Office found that ditching efavirenz for dolutegravir would double the percentage of new infections averted between 2019 and 2038 in South Africa.
But an August health department circular says that although the country will “ceremonially launch” the dolutegravir on World Aids Day in December, a three-drug combo containing the wonder ARV won’t be in patients’ hands until January at the earliest.
Meanwhile, provincial depots have been instructed to stop delivering the medication to clinics. The health department is confident it will have enough efavirenz-based treatment to carry the country over until it can begin switching patients who have been on treatment for six months or more, and who are virally suppressed, onto the newer drug.
Contraception won’t be a pre-requisite for access to new drug
Fears about the as-yet unconfirmed risk of birth defects tied to the drug prompted some countries to consider making access to dolutegravir contingent on birth control use among women. Around the world, activists were outraged by the proposition, saying it was paternalistic and negated women’s abilities to weigh up the information and decide for themselves which drug was right for them — and the WHO agreed.
Meg Doherty is the WHO’s coordinator of treatment and care for HIV, hepatitis and sexually transmitted infections. This is how she said she’d explain the WHO’s new thinking on dolutegravir to women:
“I would say that neural tubal defects occur in all pregnancies and can be related to many things other than drugs… diabetes, being overweight…The benefits of taking dolutegravir for [standard HIV] treatment outweigh the harm.
“But there should be an individual discussion with the young woman, especially if she is interested in becoming pregnant, about her understanding of… the small and potentially real risk of a neural tube defect.”
Doherty concluded: “She could also consider taking another drug if she felt that it would be better for her.”
National Health department spokesperson Popo Maja confirmed that the country’s new draft ARV guidelines won’t make access conditional based on contraceptive use for women. Instead, the guidelines — and training materials for healthcare workers — say women should be provided with all the information they need to make an informed choice. They are also likely to say that anyone taking the new drug should be advised to eat healthily and stay active to ward off weight gain — something that could apply to most of us, WHRI researcher Michelle Moorhouse told Bhekisisa earlier this year.
“Women should be fully informed with regard to the risks and benefits of using either dolutegravir and efavirenz,” Maja says.
This is something that’s already being incorporated into educational materials, being produced in four official languages, by WRHI, the Treatment Action Campaign (TAC) and the organisation HIV i-Base, which specialises in simple, easy to understand educational materials around HIV.
The TAC’s treatment literacy training coordinator Lucky Mkhondwane says that this is the second time that concerns around possible birth defects have stalled the roll out of the new ARV.
“With the transition being delayed again, the TAC has engaged the national health department along with other civil society actors,” Mkhondwane said. “We have raised concerns about the delays as healthcare users have been anticipating the transition for a long time.”
In January, South Africa may present women with HIV with a choice to pick which treatment is right for them. Part of making that choice will be making an informed decision about whether or not contraception is right for them. And if it is, what kind.
But the country has faced chronic shortages of contraception in the last two years. And, says Mkhondwane, the country will have to do better if it wants to give women a real choice about their drugs and bodies.
“In order for us to reduce the risk of possible birth defects, South Africa will have to be in a position that will allow women of childbearing [age] to make an informed choice with regards to what regimen they’d like to be on and to provide contraceptives for those women who might decide that they don’t want to fall pregnant,” Mkhondwane explains. “The government hasn’t done anything significant to remedy the over-reliance on [the three-month shot] Depo Provera.”
In the United States, Depo Provera is strictly regulated. Prescribing information approved by the Food and Drug Administration warns it should not be used for more than two years continuously because patients may see a reduction in bone density.
Attempts to distribute an upper-arm contraceptive implant called Implanon Nxt, meanwhile, led to a plethora of problems, with providers complaining that they were trained, for instance, to insert them, but not remove them. Women and doctors, meanwhile, complained that the devices were not always inserted correctly and even moved around after being implanted.
The country’s latest HIV strategic plan aims to provide contraception to about 75% of women between the ages of 15 and 49 who want it by 2020/21.
“The large scale rollout of the implant, Implanon Nxt, was not really well thought out and with all the adverse events reported, led to a lot of women removing it,” Mkhondwane adds. “It showed us that health facilities were ill-prepared for the rollout.”