By Kate O’Rourke
Once-daily bictegravir-emtricitabine-tenofovir alafenamide (BIC/FTC/TAF; Biktarvy, Gilead) may be appropriate to use without dose adjustment during pregnancy, according to a study led by scientists at Gilead (AIDS 2024;38[1]:F1-F9).
The combination of BIC/FTC/TAF is approved as a guideline-recommended, once-daily, single-tablet complete regimen for the treatment of HIV-1 infection. BIC/FTC/TAF treatment leads to high rates of virologic suppression in treatment-naive people with HIV and maintains virologic suppression among people switching from other antiretroviral therapy regimens. However, limited data exist regarding BIC/FTC/TAF use during pregnancy; therefore, use in pregnant women is not included in the product label.
This study was an open-label, multicenter, single-arm, phase 1b study in 33 virologically suppressed pregnant women with HIV-1. Participants received BIC/FTC/TAF from the second or third trimester through approximately 16? weeks’ postpartum. The researchers collected steady-state maternal plasma pharmacokinetic samples at the second and third trimesters and six and 12? weeks’ postpartum for BIC, FTC and TAF. Neonates (n?=?29) were followed from birth to 4 to 8 ?weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The researchers evaluated the proportion of participants with HIV-1 RNA less than 50? copies/mL at delivery.
The researchers found that the mean areas under the concentration–time curve over the dosing interval (AUCtau) for BIC, FTC and TAF were lower during pregnancy versus postpartum but were closer to AUCtau values for nonpregnant adults with HIV reported in other studies. Geometric least squares mean ratios for BIC, FTC and TAF AUCtau during pregnancy versus postpartum ranged from 41% to 45%, 64% to 69% and 57% to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 hours. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission.
The researchers said pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggests that once-daily BIC/TAF/FTC without dose adjustment is appropriate during pregnancy.
“This study from the manufacturer of Biktarvy is important, as it provides some of the first pharmacokinetic data on BIC/TAF/FTC use in the second and third trimester of pregnancy and postpartum period,” said Ethel D. Weld, MD, PhD, an assistant professor of medicine, pharmacology and molecular sciences, Division of Clinical Pharmacology, Division of Infectious Diseases, Department of Medicine, at The Johns Hopkins University School of Medicine, in Baltimore, who was not involved with the study.
“My most important takeaway is that these 32 pregnant women (after excluding one participant who was found to be an enrollment violation because of baseline resistance to components of the regimen), after switching to a regimen of once-daily BIC/TAF/FTC in the second or third trimester of pregnancy, maintained 100% HIV viral suppression throughout their pregnancies and the postpartum period, and there were no perinatal HIV transmissions. In that setting, it appears that antiretroviral drug concentrations, while substantially lower in the second and third trimester of pregnancy than in the postpartum period in the same women (and also lower than in nonpregnant adults), were high enough to work,” she said, adding the data during pregnancy, “increases my clinical comfort with using BIC/TAF/FTC in pregnancy.”
—Dr. Weld reported no relevant financial disclosures.