Bictegravir’s pharmacokinetics appear promising for ART in pregnancy
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Finding antiretroviral therapy that is both safe and effective in pregnant people is essential to ending mother-to-child transmission and pediatric HIV infection. An initial study looking at integrase inhibitor-based regimens raised some concern about an increased risk of neural tube defects when dolutegravir was given during the first trimester of pregnancy. Subsequent data have not replicated this risk, and the U.S. Department of Health and Human Services now lists dolutegravir as a first-line option in pregnancy or for those trying to conceive. These same guidelines do not give any recommendations for bictegravir, or BIC, due to the lack of pharmacokinetic data. Because it’s well known that pregnancy brings physiologic changes that can influence drug levels, the lack of PK data creates doubt and concern that months of low levels will put people at risk of impending viral resistance.
In an article recently published in AIDS, 33 virologically suppressed pregnant women (three from the Dominican Republic, 25 from Thailand and five from the United States) were given bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) from the second or third trimester through about 16 weeks postpartum. The investigators evaluated steady-state maternal plasma PK levels throughout the pregnancy and postpartum for each of the ART components along with the maternal viral load at delivery. BIC exposure was similar throughout pregnancy but slightly lower than levels postpartum. The mean area under the concentration-time curve over the dosing interval was lower during the pregnancy than after, and compared to nonpregnant adults with HIV, was about 40% lower. Similar findings were seen with FTC and TAF, and only BIC was found to cross the placenta with a half-line in neonates of 43.1 hours. Importantly, the mean trough concentration for BIC throughout pregnancy was much greater than the required protein-adjusted 95% effective concentration for BIC, meaning that the lower AUC still kept the study participants above the level needed for efficacy.
Importantly, virologic suppression was maintained in 100% of participants at delivery and up to a median of 16 weeks postpartum. There was no virologic failure or treatment-emergent resistance, and CD4 cell counts and percentages were stable throughout. Based on these findings, BIC/FTC/TAF appears to be a reasonable single-tablet option for pregnant people with HIV.
