An observational study in Botswana showed no increased risk for adverse birth outcomes with dolutegravir-based antiretroviral therapy compared with an efavirenz-based regimen.
Dolutegravir, an integrase strand transfer inhibitor with superior efficacy and tolerability and a higher resistance barrier than other antiretrovirals, was introduced in Botswana in 2016 as a first-line antiretroviral therapy (ART) for all adults with HIV (including pregnant women, despite limited data). In this observational multicenter study in Botswana, researchers assessed birth outcomes among 1729 women starting a dolutegravir-based regimen compared with 4593 women initiating efavirenz-based ART during pregnancy.
Rates of adverse birth outcomes were similar among women initiating dolutegravir-based ART compared with those using an efavirenz-based regimen (33.2% and 35.0%, respectively). Risk for severe adverse birth outcomes was also similar (10.7% and 11.3%). Compared with HIV-negative women, those with HIV had higher risk for any adverse birth outcome (28.9% vs. 34.5%) regardless of ART regimen.
Reviewing Author
DisclosuresConsultant/Advisory BoardUNAIDS; WHO; Bill and Melinda Gates Foundation, Population Council
Grant/Research SupportNIH; National Institute of Allergy and Infectious Diseases; Tides Foundation/MAC AIDS Fund; USAID; South African National Research Foundation; European Union; South African Medical Research Council
Editorial BoardsNew England Journal of Medicine; AIDS Reviews; AIDS Research and Human Retroviruses; mBio; Indian Journal of Medical Research; JAIDS: Journal of Acquired Immune Deficiency Syndromes
DisclosuresConsultant/Advisory BoardUNAIDS; WHO; Bill and Melinda Gates Foundation, Population Council
Grant/Research SupportNIH; National Institute of Allergy and Infectious Diseases; Tides Foundation/MAC AIDS Fund; USAID; South African National Research Foundation; European Union; South African Medical Research Council
Editorial BoardsNew England Journal of Medicine; AIDS Reviews; AIDS Research and Human Retroviruses; mBio; Indian Journal of Medical Research; JAIDS: Journal of Acquired Immune Deficiency Syndromes
Citation(s):
Zash R et al. Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: An observational study. Lancet Glob Health 2018 Jul; 6:e804; [e-pub]. (https://doi.org/10.1016/S2214-109X(18)30218-3)
Comment
In showing that dolutegravir is safe when initiated during pregnancy, these data are reassuring and timely, especially as dolutegravir's safety has been called into question by preliminary data from the Tsepamo study suggesting that exposure to this agent at the time of conception raises risk for neural tube defects. The distinction between the two studies is important: While it may not be safe for women to conceive while receiving dolutegravir, it seems safe to start this drug later during pregnancy (i.e., ≥8 weeks after the last menstrual period, because the neural tube has already closed). Still, as the Tsepamo result could be due to chance, more data are needed. In the meantime, guidelines urge caution (NEJM JW Infect Dis Jun 22 2018; [e-pub]; multiple citations) when initiating dolutegravir in nonpregnant women of reproductive age; concomitant use of effective contraception must be ensured.