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Safety of Dolutegravir at Conception: Updated Data

In 2018, initial results from the Tsepamo study of birth outcomes in Botswanan women treated with ART during pregnancy raised questions about the safety of dolutegravir (DTG) when given at the time of conception or very early in pregnancy. Specifically, an early interim analysis found a higher proportion of neural tube defects (NTDs) in infants born to women who were taking DTG at the time of conception (0.94%) compared with women taking ART regimens that did not include DTG (0.12%). Subsequently, as the study increased in size and analyzed more births to women on ART, the prevalence of NTD in women who received DTG at the time of conception appeared lower (0.30% as of March 2019) than it had in the 2018 analysis.

At the 2020 International AIDS Conference (virtual) in July, researchers presented the latest data from the Tsepamo study. By the end of April 2020, the study team had accrued data on 3,591 births to women who received DTG at the time of conception. By the current analysis, the prevalence of NTD in infants of women on DTG at conception has dropped to 0.19% (7/3591), compared with 0.11% in infants of women on non-DTG regimens. This difference no longer is statistically significant. 

As in earlier analyses, no statistically significant difference in NTD prevalence was found between women who started DTG during pregnancy (i.e., after conception) compared with HIV-negative women.

Clinical Bottom Line

As the numbers of infants exposed to DTG at the time of conception have grown, the rate of observed NTD has decreased steadily, and no longer is significantly different from the rate of NTD in infants exposed to other ARVs. This suggests the initial safety signal may have been caused by a random cluster of NTD in the initial cohort of women treated with DTG – time and accumulation of more data on birth outcomes of women on DTG will clarify this issue.

Current HHS perinatal guidelines, last updated in April 2020 and thus based on older data, designate DTG as a “preferred“ ARV for pregnant women at any trimester, and as an “alternative” for women trying to conceive. We can anticipate revisions later this year.

In the United States, dolutegravir is marketed as Tivicay and is included in the coformulations Triumeq, Juluca, and Dovato.

Reference

Zash R et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana. AIDS 2020: 23rd International AIDS Conference Virtual. July 6-10, 2020. Abstract OAXLB0102.