Bictegravir, Emtricitabine, and Tenofovir Alafenamide Fixed-Dose Combination for Treatment of HIV in Adolescents and Children: Week 48 Results from an Open-Label, Multicentre, Phase 2/3 Paediatric Trial

Abstract

Background: Bictegravir a potent integrase strand transfer inhibitor (INSTI) with a high barrier to resistance, coformulated with emtricitabine and tenofovir alafenamide, is a guidelines-recommended and preferred single-tablet regimen for adults and adolescents. The aim of this study was to evaluate the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents living with HIV. Methods: In this prospective, multi-country, 48-week, Phase 2/3, single-arm, open-label trial (ClinicalTrials.gov, number NCT02881320), virologically suppressed children and adolescents (6 to <18 years of age) living with HIV were switched from their current regimen to bictegravir, emtricitabine, and tenofovir alafenamide (50/200/25 mg) once daily. Predicted systemic exposures (area under the curve and concentration at the end of the dosing interval [AUC tau and C tau ]) of bictegravir and safety assessments (adverse events) were co-primary outcomes and compared with adult values. Findings: Between September 29, 2016 and February 16, 2018, 102 participants were enrolled. One hundred received bictegravir, emtricitabine, and tenofovir alafenamide (6 to <12 years: n=50; 12 to <18 years: n=50). Bictegravir C tau was 35% lower in adolescents and bictegravir C max was 53% higher in children, compared to adults. However, no clinically relevant differences in bictegravir, emtricitabine, and tenofovir alafenamide exposures were observed in adolescents and children compared with adults. With median duration of exposure to study drug of 80 weeks, bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were <= grade 2 and there were no study drug-related serious adverse events. Only one individual discontinued study drug due to adverse events (grade 2 insomnia and anxiety). All 100 participants had HIV-1 RNA <50 copies per mL at week 24 and 98% (98/100) at week 48; no participant had treatment-emergent resistance. Interpretation: In adolescents and children living with HIV, the adult-strength bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virologic suppression. No clinically meaningful drug exposure differences comparing to phase 3 trials in adults were noted. Study data support the treatment of HIV in adolescents and children with bictegravir, emtricitabine, and tenofovir alafenamide. This single-tablet regimen offers an important regimen for adolescents and children living with HIV with the attractive attributes of having a high barrier to resistance, small tablet size, low potential for drug-drug interactions, and lack of food requirement. Trial Registration: This study is registered with ClinicalTrials.gov, number NCT02881320. Funding Statement: Gilead Sciences, Inc. Declaration of Interests: I was a stockholder and employee of Gilead Sciences at the time the clinical study described in the manuscript was conducted and when manuscript was written. Ethics Approval Statement: This trial was undertaken in accordance with the Declaration of Helsinki and approved by central or site-specific review boards or ethics committees. In the native language, all participants (7 to <18 years of age) were required to provide written or oral assent, and their parents/caregivers provided written informed consent.