681Pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed pregnant women with HIV

H. Zhang¹, H. Martin¹, L. Lin¹, M. Davis¹, H. Huang¹, D. Xiao¹, P. Arora¹, A. Avihingsanon², E. Koenig³, R. Palaparthy¹, S. Girish¹, D. Marathe^{1 1}Gilead Sciences, Inc., Foster City, United States, ²HIV-NAT, Thai Red Cross AIDS Research Centre and CE of Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, ³Dominican Institute of Virological Studies (IDEV), Santiago, Dominican Republic

BACKGROUND: Safe, effective, and convenient treatment options are needed for pregnant women with HIV. Bictegravir (BIC) is highly protein bound and metabolized by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and cytochrome P450-3A4 (CYP3A4). Physiological changes during pregnancy, including increased CYP3A4 and UGT1A1 activities, have been reported; however, limited data exist on B/F/TAF pharmacokinetics, safety, and efficacy during pregnancy.
METHODS: A dedicated open-label study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1. Steady-state plasma samples were collected over 24 hours following oral administration of B/F/TAF during second and/or third trimesters of pregnancy, and 6 and 12 weeks postpartum. For BIC and TAF, protein binding was measured and serial sparse samples collected in neonates. Geometric least-squares mean (%GLSM) ratios were calculated for pharmacokinetic comparisons between pregnancy and postpartum samples. Plasma HIV-1 RNA and trough peripheral blood mononuclear cell (PBMC) tenofovir diphosphate (TFV-DP) levels were measured. The proportion of participants with HIV-1 RNA <50 copies/mL (missing=excluded) at delivery was calculated.
RESULTS: GLSM values for plasma B/F/TAF were lower during pregnancy versus postpartum (%GLSM ratios <100). For BIC and TAF, %GLSM ratios were higher when adjusted for protein binding, although they remained lower during pregnancy (Table). Trough PBMC TFV-DP levels were generally similar during pregnancy and postpartum. All pregnant women maintained virologic suppression, with HIV-1 RNA <50 copies/mL at delivery (n=32 [100%]). In neonates, median (IQR) BIC half-life was 43 (38, 58) hours, and TAF was below the quantitation limit in all neonates. There were no adverse events (AEs) leading to premature discontinuation and no drug-related AEs in pregnant women or neonates.


CONCLUSIONS: Despite the comparatively lower exposure to BIC, emtricitabine, and TAF during pregnancy versus postpartum, all adult participants maintained virologic suppression, and B/F/TAF was generally well tolerated, suggesting appropriateness for use of B/F/TAF during pregnancy and indicating that no dose change is needed.