Dolutegravir: aka women’s ‘forbidden drug’

By Matteo Cassolato

Dolutegravir, a potent and well-tolerated antiretroviral medicine recommended by the World Health Organization (WHO) as the preferred treatment option for people living with HIV has turned into a forbidden drug for many women living with HIV.

Child's ankle©Jenny Matthews for the Alliance 

Since its approval by the US Food and Drug Administration, in August 2013, dolutegravir, often known as DTG, quickly established itself as one of the best available antiretroviral (ART) medicines to treat HIV.

Dolutegravir is superior to its ‘predecessor’ efavirenz in many aspects. It achieves viral suppression faster than efavirenz; it copes better with poor adherence meaning that it’s good at preventing the development of drug resistance; and its side effects are better-tolerated.

Until last year, due to its high cost, fixed-dose combinations of ART that included dolutegravir were mainly prescribed in Western Europe, Northern America and Australia. However, thanks to a very much-needed new price agreement signed with pharmaceutical companies in September 2017, dolutegravir is on its way to the countries that most need it. It is estimated that in low- and middle-income countries, up to 15 million people might be taking dolutegravir in the next five years.

As of September 2018, over 20 low- and middle-income countries had initiated procurement for the fixed dose combination that contains dolutegravir, which replaces the fixed dose combination containing efavirenz. Kenya, Malawi, Nigeria, Uganda, and Zambia are among the countries who have already received first shipments and who have already initiated the complex process of transitioning people living with HIV from the old regimen to the improved one.

Concerns over safety

So far, dolutegravir seems like a success story - albeit tainted by the notorious delays with which innovation reaches those who most need it and who can’t afford it - and one that could truly transform the epidemic.

Sadly, this is not the case. In May 2018, WHO and other agencies raised safety alerts concerning women’s use of dolutegravir at the time of conception. The alerts have since then affected low- and middle-income country’s plans to introduce dolutegravir-based treatment for women living with HIV, turning the long awaited wonder medicine into a veritable forbidden drug.

These safety concerns were prompted by the release of preliminary data from an observational study assessing the safety of dolutegravir during pregnancy in Botswana (the now famous Tsepamo Study). The study found four cases of neural tube defects out of 426 women who became pregnant while taking dolutegravir. The study will continue to collect data until March 2019 to either confirm or refute the safety concern.

In its initial statement, WHO asked countries to consider providing women of childbearing age only ART medicines for which adequate efficacy and safety data are available, noting that efavirenz–based regimens are safe and effective. The statement continued saying that countries should consider dolutegravir only when consistent contraception can be assured.

But Ministries of Health in low- and middle-income countries have interpreted the statement in various ways. In some, guidance has been rapidly revised to prescribe dolutegravir to women living with HIV (of childbearing potential) only when long-term contraception can be provided. In some others, dolutegravir is completely denied, recommending efavirenz in its place.

A recently published policy brief by Health Gap well describes what is happening in East and Southern Africa and reports that “following the WHO caution many countries have taken a conservative approach on women’s access to DTG, and in some cases slowed or stalled progress altogether”.

The right to an informed choice

Rightly, women living with HIV have mobilised and strongly opposed any approach that does not take into consideration women’s right to make an informed choice about which HIV treatment option to take. Among many others, the voice of Martha Akello, from the International Community of Women Living with HIV Eastern Africa (ICWEA), at AIDS 2018 in Amsterdam clearly stated, “Women of reproductive age have differing needs and priorities when it comes to antiretroviral treatment. What works for one woman may not work for another”.

In addition, besides the fact that not all women may wish to have children, it must be understood that women of childbearing potential are first and foremost people in their own right, with very specific reproductive health desires and needs. This includes understanding and accepting that there can be (and there should be) women who opt to take dolutegravir while choosing not to use any contraception.

Since the release of its statement, WHO has expanded its position on the matter, calling for national HIV programmes to carefully consider the context, balancing benefits and risks when deciding what the optimal ARV regimens for women living with HIV are. WHO also called for a woman-centred approach that respects women’s autonomy in decision-making about their own health.

Despite the fact that civil society groups such as AfroCAB have reacted rapidly, issuing their own statement and calling for dolutegravir to be “made available urgently across the continent with everyone having access”, with some exceptions , the situation today has not much improved.

Women living with HIV in many low- and middle-income countries are not free to access dolutegravir the way they prefer. Once again, policy making instead of supporting the ability of women to make meaningful choices, decides for them, imposing sacrifices and limits to what they can do with their own bodies.

Thankfully, new data that recently became available at the International Congress on Drug Therapy in HIV infection in Glasgow, shows no further evidence of increased risk of birth defects associated with dolutegravir. To obtain more conclusive evidence, the global HIV community will have to wait until March 2019 for the final results of the Botswana Tsepamo study.

However, as correctly pointed out by many women’s reproductive and sexual health advocates, there is a silver lining. The dolutegravir story gives us the opportunity to effectively plan for real integration between sexual and reproductive health and rights services, and HIV treatment, finally turning plans into practice.