Virologic suppression maintained through pregnancy and postpartum with B/F/TAF
Presenter: Dhananjay Marathe, PhD, Gilead Sciences, Foster City, Calif.
Pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed pregnant women with HIV. Presented July 24, 2023.
Once-daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is suitable for use throughout pregnancy, including the second and third trimesters, without a need for dose change, according to a pharmacokinetic study performed in virologically suppressed pregnant women with HIV.
“All 32 adult participants had fewer than 50 HIV-1 RNA copies per mL of blood at delivery and maintained virologic suppression through 18 weeks postpartum, with no observed virologic failure or treatment-emergent resistance,” said presenter Dhananjay Marathe, PhD, Gilead Sciences, Foster City, Calif.
Safe, effective, and convenient treatments are needed for pregnant women with HIV. B/F/TAF is approved for treatment in people with HIV-1, but limited data exist on its pharmacokinetics, safety, and efficacy during pregnancy, prompting a dedicated study in this population, he said. “Bictegravir is highly protein-bound and metabolized by UGT1A1 and CYP3A4, and we know that there is increased activity of both of these enzymes and other physiological characteristics (ie, protein binding) during pregnancy.” To this end, the investigators evaluated once-daily fixed dosing in an open-label study in pregnant women living with HIV-1, all of whom were virologically suppressed (HIV-1 RNA < 50 copies/mL) at the start of the study.
Steady-state plasma samples were collected over 24 hours following once-daily oral administration (50/200/25 mg) during the second and/or third trimesters of pregnancy, and at 6 and 12 weeks postpartum.
The main objective was to evaluate steady-state pharmacokinetics of bictegravir, emtricitabine, and tenofovir alafenamide and maintenance of HIV-1 virologic suppression. Cord blood samples for bictegravir and tenofovir alafenamide were also collected at delivery. The primary endpoint was bictegravir’s area under the plasma concentration-time curve between the 24-hour dosing intervals (AUC tau) during pregnancy and postpartum.
Bictegravir plasma exposures were similar between the second and third trimesters and between 6 and 12 weeks postpartum. Exposure was reduced during the second and third trimesters compared with 6 and 12 weeks postpartum. “Despite these differences, the individual trough concentration values were more than IQ1 (inhibitory quotient at protein-adjusted 95% effective concentration), which is indicative of efficacious exposures in all participants during pregnancy, except in a single participant in the second trimester only, who importantly remained virologically suppressed throughout the study,” said Dr. Marathe. “Moreover, the median trough concentrations were approximately 7- and 6-fold of IQ1 during the second and third trimesters.”
The total bictegravir AUC tau was 59% lower during the third trimester than 12 weeks postpartum, and the unbound bictegravir AUC tau was calculated to be 41% lower in the third trimester versus 12 weeks postpartum. “Exposure levels [of bictegravir] in pregnancy are closer to those in nonpregnant adult people with HIV,” he said. “The mean total bictegravir AUC tau in the third trimester was 41% lower than values reported in nonpregnant adult people with HIV.” Both plasma emtricitabine and plasma tenofovir alafenamide exposures were lower during pregnancy compared with postpartum.
CD4 cell counts and CD4% remained stable for adult participants through postpartum. The median CD4 cell count at baseline was 558/µL, with a median change of 159/µL by 12 weeks postpartum.
In neonates, the median bictegravir half-life was 43 hours, which is longer than that in adults, and tenofovir alafenamide was below the quantitation limit in all neonates.
Virologic suppression was maintained during pregnancy, delivery, and through week 18 postpartum: all (32/32) adult participants had fewer than 50 HIV-1 RNA copies per mL at delivery and through week 18 postpartum. No virologic failure or treatment-emergent resistance was observed. All 29 neonates enrolled were negative for HIV by polymerase chain reaction.
There were no discontinuations due to adverse events. One instance of neonatal asphyxia (grade ≥ 3) was observed, and one false labor in an adult. Six serious adverse events were recorded in adults and 5 in infants. The most common adult adverse events were gestational diabetes, preeclampsia, and anemia. Adverse events in newborns included neonatal jaundice and respiratory distress.
Dr. Marathe is employed by Gilead Sciences and has restricted stock ownership.