Expectant mums’ use of dolutegravir safe for babies

Treatment with dolutegravir during pregnancy does not appear to pose an excess risk of adverse birth outcomes, according to two studies presented at the 24th International AIDS Conference in Montreal, Canada.

In the DOLOMITE-NEAT ID Network study, there were no significant differences in the frequency of birth defects observed between women exposed to dolutegravir during the first trimester of pregnancy and those with second-to-third trimester exposures (4.8 percent vs 2.1 percent; p=0.652). Additionally, there were no neural tube defects in each group. [AIDS 2022, abstract 6781]

More importantly, most women achieved viral suppression (<200 copies of HIV per millilitre of blood; 91 percent), and none of the infants contracted HIV, said one of the study authors, Dr Justyna Kowalska from the Medical University of Warsaw in Warsaw, Poland.

The analysis included 138 women (median age 32 years, 40.6 percent White) from Canada and several countries across Europe who had been exposed to dolutegravir during pregnancy, including 92 in the first trimester and 46 in the second/third trimester. The median cumulative exposure was 96 days.

At baseline, 91 (65.9 percent) women had undetectable viral load (<50 copies/ml). In terms of pregnancy outcomes, a total of 120 women gave birth to 131 live neonates (eight multiples), two experienced stillbirths, and 16 had miscarriages or induced abortions.

“Dolutegravir shows high penetration across the placenta, suggesting protection against infant HIV infection but potential increased adverse birth outcomes,” Kowalska pointed out, adding that while the numbers are too small to make definitive conclusions, the current findings provide reassurance that dolutegravir exposure during pregnancy is relatively safe.

Dolutegravir vs efavirenz

Kowalska and colleagues’ data are also consistent with that obtained in the second study, which did not find any clear signal of neural tube defect risk as well as increased incidence of adverse pregnancy outcomes among women who were periconceptionally exposed to dolutegravir vs efavirenz.

There were no cases of neural tube defects documented in the entire cohort, but there was one case of cleft lip and palate in the efavirenz group. As for the frequency of other outcomes, the dolutegravir and efavirenz groups had comparable incidence of preterm delivery (9.6 percent vs 12.0 percent; p=0.46), small for gestational age (16.2 percent vs 13.3 percent; p=0.41), and stillbirth (3.0 vs 1.3 percent; p=0.24). [AIDS 2022, abstract 10418]

The analysis included 198 women periconceptionally exposed to dolutegravir and 398 matched women periconceptionally exposed to efavirenz in Kenya. The median age of the entire cohort was 34.8 years. Most women were married (76.4 percent), finished at least high school (59.3 percent), and did not work outside of home (83.7 percent).

Attendance to antenatal care was high overall, and viral suppression rates were similar in the dolutegravir and efavirenz groups. Likewise, the prevalence of risk factors for neural tube defect was not significantly different, except for the history of seizures (present in one woman taking dolutegravir) and diabetes mellitus (0.7 percent vs 0.4 percent; p<0.01).

“Previous studies suggested an association between periconceptional dolutegravir use among women of childbearing age and neural tube defects the offspring. This safety signal prompted countries to delay or suspend plans to transition [such women] to dolutegravir regimens,” according to first study author Juliana Da Silva, a biologist at Centers for Disease Control and Prevention in Atlanta, Georgia.

“While the initial safety signal observed was not confirmed in subsequent data, many countries continued to be hesitant to use dolutegravir in women of childbearing age,” Da Silva added.

Taken together, the two studies presented contribute to the evidence base of dolutegravir’s safety in pregnant women and those who are planning to conceive, as well as support current World Health Organization guidelines to use dolutegravir as a preferred first-line antiretroviral drug in all populations.