Background:
Bictegravir (BIC) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity. It is highly protein bound (~99.7%) and eliminated by UGT1A1 and CYP3A metabolism. Although protein binding and hepatic enzyme activity are altered during pregnancy, limited data exist on BIC pharmacokinetics (PK) in pregnancy. We describe preliminary BIC PK in pregnancy compared to postpartum and associated virologic outcomes.
Methods:
IMPAACT 2026 is an ongoing, nonrandomized, open-label, parallel-group, multi-center phase-IV prospective study of antiretroviral PK in pregnant women with HIV. Intensive steady-state 24-hour PK sampling of oral BIC 50 mg once-daily (a component of Biktarvy®) and HIV viral load testing were performed during the 2nd and 3rd trimesters (2T, 3T), and 6-12 weeks postpartum (PP). Total BIC concentrations were measured by a validated LC-MS/MS assay, quantitation limit of 0.078 mcg/mL. Geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated between 3T vs. PP.
Results:
Preliminary analysis, triggered by low PK exposures, included 17 participants, 16 from the United States and 1 from Thailand (9 Black, 3 white, 1 Native American/Alaskan Native, 1 Asian and 3 unknown; 41% Hispanic/Latina; median entry age 31.0 years [interquartile range 25.8, 36.7]). BIC PK data were available for 6, 13, and 5 participants in 2T, 3T and PP. Compared with paired postpartum data (n=5), BIC AUCtau was 60% lower and Cmax was 53% lower in 3T (Table 1). All C24 concentrations were above the estimated BIC protein-adjusted EC95 value of ~0.162 mcg/mL. Nine of 13 women had a 3T BIC AUCtau < the prespecified target, the 10th percentile for non-pregnant persons (58.7 mcg*hr/mL). Viral suppression (< 40 copies/mL) was achieved in 5/6, 12/13, and 4/5 participants at 2T, 3T and PP, respectively. The same participant had detectable viral loads at all three timepoints despite exceeding the 10th percentile BIC AUCtau for non-pregnant persons.
Conclusions:
Total BIC exposures were lower during pregnancy compared to postpartum, yet all C24 concentrations were greater than the BIC EC95. Viral suppression was maintained in pregnancy and postpartum. As physiological changes during pregnancy can reduce drug protein binding, increased unbound BIC concentrations combined with the high potency of BIC may have contributed to observed viral suppression. Study enrollment is ongoing with collection of additional BIC PK results (including unbound concentrations), safety, and clinical outcomes.