Graeme Meintjes

Dolutegravir is a preferred drug for inclusion in ART regimens given its tolerability, efficacy and high resistance barrier. A recent safety concern of excess neural tube defects (NTDs) in infants born to mothers who conceived while on dolutegravir has been reported. This session reviewed that data and its implications.

The Tsepamo study ascertains birth outcomes at 8 sites across Botswana. Recently, it was reported that four infants with NTDs were born to women who conceived while taking dolutegravir. The neural tube closes in the first 28 days of pregnancy; making this the risk period for NTDs. Updated Tsepamo data show that these four NTDs occurred among 596 women who conceived on dolutegravir (incidence = 0.67%, 95%confidence interval=0.26%-1.7%). The risk in women conceiving on non-dolutegravir regimens was 0.12% (95%confidence interval=0.07%-0.21%); confidence intervals do not overlap. This an early signal; more data is required to confirm or refute whether dolutegravir is definitely associated with higher risk for NTDs. This risk, if confirmed, also needs to be weighed against dolutegravir’s benefits: a modelling study suggested that dolutegravir-based ART would avert >25,000 deaths among women of childbearing age and 5,000 pediatric HIV infections compared to efavirenz-based ART over five-years in South Africa.

Updated WHO guidelines released this week advise dolutegravir as a preferred drug in first-line, an option in second-line and third line ART. It is advised that women of childbearing potential who do not currently want to become pregnant can receive dolutegravir together with consistent and reliable contraception. Speakers in the session emphasised that until further data is available, caution should be exercised to avoid conception occurring in women taking dolutegravir; women should be engaged in decision-making regarding ART choices while being provided with information of the risks and benefits of dolutegravir, and ready access to reliable and effective contraception.