Objective:

The objective of this study was to assess the pharmacokinetics (PK), safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy.

Design:

An Open-label, multicenter, single-arm, Phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1.

Methods:

Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma PK samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC and TAF. Neonates (n = 29) were followed from birth to 4-8 weeks with sparse washout PK sampling for BIC and TAF. The proportion of participants with HIV-1 RNA <50 copies/mL at delivery (missing = excluded) was evaluated.

Results:

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 non-pregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC and TAF AUCtau during pregnancy versus postpartum ranged from 41-45%, 64-69% and 57-78%, respectively. Mean BIC trough concentrations during pregnancy were >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 due to adverse events, and no perinatal transmission.

Conclusions:

Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. PK and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.