The risk of neural tube defects linked to dolutegravir exposure during pregnancy is lower than previously signaled, according to new reports that have prompted the World Health Organization (WHO) to confirm that this antiviral medication should be the preferred option across all populations.

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The use of dolutegravir (DTG) during pregnancy has been a pressing global health question since May 2018, when an unplanned interim analysis of the Tsepamo surveillance study of birth outcomes in Botswana showed four neural tube defects associated with dolutegravir exposure among 426 infants born to HIV-positive women (0.94%).

With follow-up for additional births, however, just one more neural tube defect was identified out of 1,683 deliveries among women who had taken DTG around the time of conception (0.30%), according to a report just presented here at the at the International AIDS Society Conference on HIV Science.

By comparison, prevalence rates of neural tube defects were 0.10% for mothers taking other antiretroviral therapies at conception, 0.04% for those specifically taking efavirenz at conception, and 0.08% in HIV-uninfected mothers, according to the report, which was simultaneously published in the New England Journal of Medicine.

“While there may be a risk for neural tube defects, this risk is small, and really importantly, needs to be weighed against the large potential benefits of dolutegravir,” investigator Rebecca M. Zash, MD, of Beth Israel Deaconess Medical Center, Boston, said here in Mexico City during an IAS 2019 video press conference.

The WHO had previously sounded a note of caution, saying that DTG could be “considered” in women of childbearing age if other first‐line antiretroviral agents such as efavirenz could not be used.

However, following release of new evidence, including the study by Dr. Zash and colleagues, the WHO has come out with a clear recommendation for HIV drug as “the preferred first-line and second-line treatment for all populations, including pregnant women and those of childbearing potential.”

The updated scientific reports and guidelines have important implications for global health. “Many countries have been working to make dolutegravir-based treatment their preferred first-line regimen, as it’s got several advantages over efavirenz, which people have been using for many years now, including its tolerability and resistance profiles, and its impact on morbidity and mortality,” IAS president Anton Pozniak, MD, said in the press conference.

Some countries paused their plans to roll out dolutegravir-based regimens after the preliminary safety signal from the Tsepamo study was reported, Dr. Pozniak added.

In another study presented at IAS looking at dolutegravir use at conception, investigators described an additional surveillance study in Botswana, conducted independently from the Tsepamo study. One neural tube defect was found among 152 deliveries in mothers who had been taking DTG at conception (0.66%), and two neural tube defects among 2,326 deliveries to HIV-negative mothers (0.09%).

Although the number of deliveries are small in this study, the results suggest a risk of neural tube defects with DTG exposure at conception of less than 1%, said Mmakgomo Mimi Raesima, MD, MPH, public health specialist, Ministry of Health and Wellness, Botswana.

Because neural-tube defects might be related to low folate levels, Dr. Raesima said “conversations are continuing” with regard to folate food fortification in Botswana, a country that does not mandate folate-fortified grains.

“We want to capitalize on the momentum from these results,” Dr. Raesima said in the press conference.

The Tsepamo study was funded by the National Institutes of Health. Dr. Zash reported grants during the conduct of the study from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

SOURCE: Zash R et al. N Engl J Med. 2019 Jul 22. doi: 10.1056/NEJMoa1905230.

New WHO recommendations promote dolutegravir benefits in the face of lowered risk signal for neural tube defects