Dolutegravir, contraception and women’s choice

In new interim treatment guidelines released by the World Health Organization (WHO) at the International AIDS Conference (AIDS 2018) in Amsterdam last week, HIV wonder drug, dolutegravir (DTG), is promoted to the preferred drug of choice for all people living with HIV starting first- and second-line treatment. 

DTG’s profile is impressive. Both powerful and potent, it can be used in all populations, reduces viral load rapidly, has minimal side effects, and HIV has a difficult time becoming resistant to it. 

But its status as the ‘golden child’ of HIV treatment options was marred slightly in May when the WHO released a security warning cautioning its use in women wishing to conceive following evidence from Botswana of a potential link to birth defects. 

In their new guidelines, the WHO state that they are taking the Botswana evidence seriously, but there is limited evidence to warrant a change in guidance. For women of childbearing potential, they should be counselled about a potential risk and given access to effective contraception. For women wishing to conceive or without access to regular and effective contraceptives, they can consider reverting to the original 2016 treatment guidance – which calls for an efavirenz (EFV)-containing regime. 

In relation to the evidence, preliminary data from the Tsepamo study presented at the conference found four cases of neural tube defects out of 426 women who became pregnant while taking DTG. This is a rate of 0.9% compared to a 0.1% risk of neural tube defects in infants born to women taking other antiretroviral medicines at the time of conception. That equates to around 1 in 100 as opposed to 1 in 1,000.

While concerning no doubt, the safety concern only related to women on DTG at the time of conception, and not at any other time in pregnancy. In fact, results presented at AIDS 2018 from the DolPHIN study showed DTG to be superior for reducing viral load in those starting treatment in their third trimester. 

The potential safety issue relating to DTG in May solicited a varied response from countries. Some countries proceeded with caution, others with haste. In Kenya and Zimbabwe, DTG was removed as an option for all women living with HIV of a childbearing age, regardless of whether they wanted children or were on effective contraception. 

Interestingly, when efavirenz was first rolled-out, its use was also not recommended for pregnant women living with HIV because of an elevated risk of birth defects. But these risks were eventually weighed up against the benefits of efavirenz over nevirapine (NVP) - with EFV having far superior viral suppression rates while also being more tolerable.

At AIDS 2018, the voices of women living with HIV were clear, “blanket exclusions that deny women equitable access to this optimal HIV treatment are not warranted or justified,” said Jacque Wambui of the Kenyan National Network of People Living with HIV and AIDS. In her presentation at AIDS 2018, Wambui condemned the lack of involvement and consultation of women living with HIV in governments’ decision to limit access to DTG. 

“It is critical to not just view a pregnant mother, or any woman of childbearing potential, as a vessel for a baby, but as an individual in her own right, who deserves access to the very best, evidence-based treatment available and the right to be adequately informed to make a choice that she feels is best for her.”

In sub-Saharan Africa, the proportion of women aged 15-49 reporting use of a modern contraceptive method is just 29%. In the same session, Chelsea Moroni from the Botswana UPenn Partnership and the Liverpool School of Tropical Medicine responded to a question from the floor about contraception for women living with HIV in sub-Saharan Africa:

“In some ways [it’s] very frustrating that it’s taken this particular issue to catalyse interest in this important area. Unmet need for effective contraceptive care for women, and particularly women living with HIV, is something we have been aware of for a very long time. The silver lining is now that there is interest, and there is an excellent opportunity to upscale the provision of the most highly effective methods of contraception to those who need them... We need to operationalise this with urgency.” 

The consensus on dolutegravir, however, is clear. Given current evidence, the benefits of DTG far outweigh any potential risks, and they should not derail the roll-out of the wonder drug across low- and middle-income countries. In terms of closing the gap on contraceptive access, it’s hoped the new DTG advice will propel a more integrated HIV and sexual reproductive health rights (SRHR) agenda for women living in lower resourced contexts.