Dolutegravir treatment around the time of conception is not associated with an increased risk of neural tube defects in infants exposed to the drug at the time of conception, the most recent surveillance report from Botswana’s Tsepamo study has concluded. Indeed, the prevalence of neural tube defects in infants exposed to dolutegravir shows a downward trend compared with earlier surveillance periods, say the investigators.
The findings, presented as a late-breaker poster at the 24th International AIDS Conference (AIDS 2022), confirm study updates provided in 2019 and 2020 and provide further reassurance that women of childbearing potential can receive dolutegravir-based antiretroviral treatment in the same way as other adults and children.
Concerns about the potential for neural tube defects in infants exposed to dolutegravir arose as a result of a surveillance study in Botswana. In 2018, preliminary data from the Tsepamo study suggested a slightly raised risk of neural tube defects in infants exposed to dolutegravir at the time of conception compared to those exposed to efavirenz or to infants of mothers without HIV.
Regulatory authorities in the United States and European Union issued safety warnings regarding the need for women of childbearing potential to use effective contraception if they were taking dolutegravir. Subsequent World Health Organization guidance stressed the importance of consistent and reliable contraception if women of childbearing potential opted to take the drug.
In response to these warnings, numerous countries in sub-Saharan Africa rapidly introduced policies that either denied dolutegravir treatment to women of childbearing potential or insisted on the need for women to use effective contraceptive methods if they were prescribed the drug.
But in 2019, follow-up surveillance data from the Tsepamo study showed that the risk of neural tube defects associated with dolutegravir was lower than first reported and the World Health Organization recommended dolutegravir-based treatment for all in its updated treatment guidelines.
Further follow-up data presented in 2020 confirmed the lack of significant difference in the risk of neural tube defects.
The preliminary findings of increased risk have affected women’s access to dolutegravir. Research published in 2022 showed that in eleven lower- and middle-income countries, women were substantially less likely to start treatment with dolutegravir than men. In countries that did not begin to implement dolutegravir-based treatment until after the safety warning in 2018, uptake of dolutegravir-based treatment in women was especially low.
At AIDS 2022, Dr Rebecca Zash and colleagues reported on surveillance in the Tsepamo study between March 2021 and March 2022. (The methodology of the study was reported here.) During the follow-up period, 32,819 live births have been recorded, including 3600 in women who were taking dolutegravir at the time of conception. Sixteen neural tube defects were identified, one in an infant exposed to dolutegravir at conception, one in an infant exposed to dolutegravir during gestation and three in infants exposed to non-dolutegravir antiretroviral therapy. The remaining eleven occurred in infants born to mothers without HIV. The prevalence of neural tube defects in infants exposed to dolutegravir at conception was 0.11%.
The difference in prevalence of neural tube defects between infants born to mothers taking dolutegravir at conception versus infants born to mothers without HIV was 0.04% (95% CI -0.01, 0.13). The difference in prevalence of neural tube defects between infants born to mothers taking dolutegravir at conception versus infants born to mothers taking efavirenz at conception was 0.03% (95% CI -0.05, 0.12). There was no difference in the rate of neural tube defects between the infants of women who took dolutegravir at conception or started it during pregnancy.
Since surveillance began in 2014, ten neural tube defects have been identified in 9460 infants exposed to dolutegravir at conception, a rate of 0.11% (95% CI 0.06, 0.19). That compares to a rate of 0.11% (95% CI 0.07, 0.16) in infants exposed to other antiretroviral therapy and 0.07% (95% CI 0.05, 0.08) in infants born to mothers without HIV.
Zash R et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo study, Botswana. 24th International AIDS Conference, Montreal, abstract PELBB02, 2022.