CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

adults, and involved starting neonates on a 5 mg once daily dose, increasing to 7.5 – 10 mg once daily after day 11. Conclusion: Dose adjustments are predicted between adult and paediatric patients. Drug approval in infants and neonates is often hindered by a lack of suitable formulations and difficulty in examining drug exposure. Several potential regimens have been identified, which are worthy of empirical investigation within this patient group.

841 B/F/TAF LOW-DOSE TABLET RELATIVE BIOAVAILABILITY IN HVs AND PK IN CHILDREN WITH HIV Sophia R. Majeed 1 , Polina German 1 , Steve K. West 1 , Shaolan S. Xiang 1 , Deqing Xiao 1 , Michael Keeney 1 , Joanna Koziara 1 , PJ Costales 1 , Jenna Scott 1 , Hiba Graham 1 , Cheryl Pikora 1 , Anita Mathias 1 1 Gilead Sciences, Inc, Foster City, CA, USA Background: Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (B/F/ TAF 50/200/25 mg) single tablet regimen (bilayer tablet) is FDA-approved for the treatment of HIV in adults and pediatrics ≥25 kg. A low-dose monolayer B/F/TAF tablet (LDT) has been developed; the relative bioavailability (rBA) and food-effect of the LDT were evaluated in a Phase 1 study. The PK of the LDT was then confirmed in children with HIV 14-< 25kg. Methods: Adult healthy volunteers (HV) received single doses of adult-strength B/F/TAF 50/200/25 mg fasted, or B/F/TAF 30/120/15 mg LDT fasted or fed (high-fat meal) in a randomized, 3-period, crossover study. PK parameters of BIC, FTC and TAF were compared between test and reference treatments using geometric least-squares mean (GLSM) ratios and 90% confidence intervals (CI) with a stringent 70-143% equivalence boundary. The PK of the B/F/TAF LDT was then assessed in virologically suppressed children ≥2 yrs, 14-<25kg (N=12) at W2. BIC exposures in children were compared to B/F/TAF-treated adults using clinically relevant boundaries of 50-200%. The PK of FTC, TAF and TAF-metabolite tenofovir (TFV) were compared descriptively to historical data. Safety was assessed throughout the studies. Results: 52/54 HVs completed the Ph1 study. GLSM ratios and 90% CIs for BIC, FTC, and TAF PK parameter comparisons between LDT and adult tablet were within 70-143% (Table). Compared to fasted, high-fat meal did not alter BIC or FTC PK; TAF AUCinf increased 42%, C max decreased 44%. 15% (adult tab fasted, or LDT fed) and 19% (LDT fasted) of HVs had an AE (all Grade 1). There were no discontinuations due to AEs. GLSM ratios and 90% CIs for BIC AUC tau and C max in children vs adults were within 50-200%. Mean BIC C tau was 32% lower (Table). Exposures of FTC (mean AUC tau =14,900 h*ng/mL), TAF (mean AUC tau =305 h*ng/ mL) and TFV (mean AUCC tau =339 h*ng/mL) were within the range of historical data. 75% had an AE (all Grade 1/2). Conclusion: B/F/TAF was well tolerated in HVs and children with HIV. The B/F/ TAF LDT provided exposures equivalent to adult tablet with no clinically relevant food-effect. Like the adult tablet, LDT can be taken without regard to food. In children 14-< 25kg with HIV taking the LDT, no clinically meaningful differences in PK were identified compared to adults; mean BIC C tau was 12-fold above paEC95, supporting its continued evaluation in pediatric trials.

840 SAFETY, PK, AND EFFICACY OF LOW DOSE B/F/TAF IN CHILDREN ≥2 YEARS OLD LIVING WITH HIV Carina Rodriguez 1 , Kulkanya Chokephaibulkit 2 , Afaaf Liberty 3 , Renate Strehlau 4 , Riana Van Zyl 5 , Pope Kosalaraksa 6 , Coleen K. Cunningham 7 , Eric J. McGrath 8 , Natella Rakhmanina 9 , Heather Maxwell 10 , Danielle Porter 10 , Sophia R. Majeed 10 , Shaolan S. Xiang 10 , Diana Brainard 10 , Cheryl Pikora 10 1 University of South Florida, Tampa, FL, USA, 2 Mahidol University, Bangkok, Thailand, 3 Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 4 Empilweni Service and Research Unit, Johannesburg, South Africa, 5 University of the Free State, Bloemfontein, South Africa, 6 Khon Kaen University, Khon Kaen, Thailand, 7 Duke University Medical Center, Durham, NC, USA, 8 Children's Hospital of Michigan, Detroit, MI, USA, 9 Children's Research Institute, Children's National Health System, Washington, DC, USA, 10 Gilead Sciences, Inc, Foster City, CA, USA Background: Few antiretroviral options exist for smaller children living with HIV and no single-tablet regimen (STR) is used or approved for this population. STR of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is approved for use in HIV-infected children weighing ≥25 kg. We report safety, pharmacokinetics (PK), and efficacy from an interim analysis of the first clinical trial of a low dose B/F/TAF tablet in young children living with HIV. Methods: Virologically suppressed children (≥2 yrs) weighing 14 to <25 kg with HIV-1 RNA <50 c/mL for ≥6 months and CD4 ≥200 cells/μL at screening, received low dose B/F/TAF (30/120/15 mg) once daily in a prospective, 48-week (W), single-arm, open-label trial. Adverse events (AE), laboratory tests, and the proportion of participants with HIV-1 RNA <50 c/mL were assessed through W12. Steady-state PK of B/F/TAF was evaluated; BIC PK in children were compared to B/F/TAF-treated adults (50/200/25 mg) using a 50-200% equivalence boundary. Results: Twelve children were enrolled; median age 6 (range 3-9) years, median weight 20.1 (range 14.6-24.1) kg, 58% female, 58% black, median CD4 count 841 cells/μL, all vertically infected. Through a median (Q1, Q3) duration of exposure to study drug of 20.1 (18.0, 27.1) weeks, most common AEs were abdominal pain, diarrhea, and upper respiratory tract infection (n=2 participants each); all AEs were grade 1 or 2; no child discontinued STR for AE. Related-AEs included neutropenia, irritability, and social avoidant behavior (n=1 each). Mean (SD) adherence to study drug was high (97.1% [7.02]). Ten of 11 (91%) children had HIV-1 RNA <50 c/mL at W12. Mean increase in CD4 count from baseline was 42 cells/mL. Geometric least squares mean ratios and 90% CIs for BIC AUC tau and C max in children vs adults were within 50-200%; BIC C tau was 32% lower (Table). FTC and TAF exposures were within the range of historical data. Conclusion: The B/F/TAF pediatric STR had high levels of adherence and virologic suppression. Exposures of all B/F/TAF drug components in young children were in the range of older populations, with mean BIC C tau 12-fold above the paEC95 for wild type virus. Efficacy and safety of the pediatric STR in young children are consistent with adult strength STR efficacy in older populations. These data support further evaluation of low dose B/F/TAF as an unboosted INSTI-based STR for young children living with HIV.

Poster Abstracts

842 MARAVIROC SAFETY & PHARMACOKINETICS IN HIV-EXPOSED NEONATES Julia C. Rosebush 1 , Brookie Best 2 , Ellen G. Chadwick 3 , Jack Moye 4 , Elizabeth Smith 5 , Kevin Butler 6 , Sarah Bradford 7 , Kyle Whitson 8 , Sisinyana R. Mathiba 9 ,

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