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Dolutegravir and pregnancy outcomes including neural tube
defects in the USA during 2008-20: a national cohort study
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Download the PDF here
Download the PDF here
and commentary: Crucial need for improved pharmacovigilance in pregnancy
No significant differences in NTD prevalence were observed between periconception dolutegravir exposure versus non-dolutegravir exposure in women with HIV, or compared with women without HIV
Despite these limitations, our study adds important information from the currently largest cohort in the USA. Our incidence estimates provide reassuring evidence that an elevated risk of infant NTD among women with HIV who used dolutegravir around the time of conception is unlikely. Associations of dolutegravir use with risk of pregnancy loss were statistically marginal and need to be further investigated in prospective surveillance or large dedicated patient cohorts. Thus, our study underscores the need for a comprehensive US system of prospective, systematic pharmacovigilance surveillance to monitor outcomes of periconceptional exposure to pharmacological agents, including antiretroviral drugs. In the absence of such a system, the pregnancy algorithm developed and used in this study with the administrative databases can still provide a robust and timely method to monitor for signals, including for rare outcomes, while minimising biases and misclassifications. Our findings are consistent with published estimates of rates of NTD and of stillbirths for the US population. The algorithm provides a method to interrogate administrative data for birth outcomes associated with newer antiretroviral drug use, and as such it fills a public health need that will become even more pressing as newer antiviral agents are licensed for use for treatment or prevention of HIV, as well as for treatment of other viral infections, such as hepatitis C or COVID-19. New antiretroviral drugs in the INSTI class, as well as in new antiretroviral drug classes, are being developed, tested, or marketed for use both as HIV treatment and pre-exposure prophylaxis. It is anticipated that millions of people worldwide might use these medications, which might have a duration of action of several months. Assuring adequate post-licensure monitoring of birth and infant outcomes for such newer antiviral agents should be a public health priority.
In this study, which includes the largest-to-date US cohort of pregnant women with HIV who used dolutegravir periconceptionally, we did not find a higher rate of NTDs among dolutegravir-exposed women with HIV than among women without HIV or women with HIV exposed to other antiretroviral drugs. Our study included 16⋅4 million directly observed livebirths (unweighted data) during 2008-20, which represents approximately one-third of all livebirths in the USA during that period.
The rate of NTDs in women with HIV and periconceptional dolutegravir exposure in MarketScan data and Medicaid data we observed is consistent with the national US rate of 0⋅07%.14
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