Lessons from dolutegravir and neural tube defects

Abstract

The relatively uncommon neural tube defects (NTDs) are among the most severe birth defects that affect an estimated 300 000 births annually. 1 Zaganjor I Sekkarie A Tsang BL et al. Describing the prevalence of neural tube defects worldwide: a systematic literature review. PLoS One. 2016; 11e0151586 Crossref PubMed Scopus (214) Google Scholar Although the causes of NTDs are multifactorial and difficult to study, folate supplementation is well established in their prevention. In this context, the 2018 announcement that preconception use of dolutegravir was associated with four NTDs in a population-based surveillance study in Botswana generated immediate and massive concern. 2 Zash R Shapiro R Neural-tube defects with dolutegravir treatment from the time of conception. N Engl J Med. 2018; 379: 979-981 Crossref PubMed Scopus (202) Google Scholar Dolutegravir was at that time poised to become the preferred first-line antiretroviral agent throughout international guidelines; the announcement sent shockwaves through the HIV world, as regulators, scientists, policy makers and people living with HIV sought to grapple with this possible association. 3 Laker EA Arinaitwe A Owarwo N et al. The potential teratogenicity alert for women conceiving on dolutegravir-based regimens: an assessment of risk communication by an urban HIV clinic in Uganda and choices made by women. Drug Saf. 2020; 43: 1133-1140 Crossref PubMed Scopus (3) Google Scholar