CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

for TBLH. Mean (SD) estimated change in glomerular filtration rate was 2.0 (20.95) mL/min/1.73m 2 . No clinically relevant differences in TAF and tenofovir exposures were observed in adolescents v. adults (Table). Most (93%, 26/28) maintained HIV-1 RNA <50 c/mL. Conclusion: FTC/TAF with boosted or unboosted third agents in HIV-infected adolescents 12 to <18 yrs had high adherence rates and was well tolerated, while demonstrating increased BMD over 24 weeks. Exposure of TAF was similar to adults. High rate of virologic suppression was maintained at W24. Findings support FTC/TAF as a safe and effective NRTI backbone in adolescents.

proportions with viral suppression and no resistance. These data support further pediatric studies of B/F/TAF, which may be an important unboosted INSTI option for HIV-infected adolescents and children due to its high barrier to resistance, small tablet size and lack of food requirement.

845 P1101: PHASEI/II STUDY OF RALTEGRAVIR CONTAINING REGIMEN IN HIV-TB COTREATED CHILDREN Tammy Meyers 1 , Paul Krogstad 2 , Pearl Samson 3 , Edward P. Acosta 4 , Jack Moye 5 , Ellen Townley 6 , Sarah Bradford 7 , Linda Marillo 8 , Laura Hovind 8 , Thucuma Sise 6 , Hedy Teppler 9 , Sylvia Dittmer 10 , Lee Fairlie 11 , Anneke Hesseling 12 , Mark Cotton 13 1 The Chinese University of Hong Kong, Hong Kong, Hong Kong, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 Harvard University, Cambridge, MA, USA, 4 University of Alabama at Birmingham, Birmingham, AL, USA, 5 National Institute of Child Health and Human Development, Bethesda, MD, USA, 6 NIAID, Rockville, MD, USA, 7 FHI 360, Durham, NC, USA, 8 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 9 Merck & Co, Inc, Palo Alto, CA, USA, 10 Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 11 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 12 Desmond Tutu TB Centre, Western Cape, South Africa, 13 Stellenbosch University, Cape Town, South Africa Background: Current antiretroviral (ARV) treatment options for children co-infected with TB and HIV-infection are limited. RIF induces UDP- glucuronosyltransferase activity accelerating the clearance of raltegravir (RAL). In adults, doubling the RAL dose partially overcame this PK interaction with no safety concerns. We sought to determine the optimal and safe dose of RAL when administered with RIF-containing anti-TB therapy in HIV-infected children. Methods: P1101 is a dose finding study for RAL for HIV-infected children receiving RIF-containing TB therapy for at least one week, with three age cohorts: Cohort 1: 2 to <6 years (closed), Cohort 2: 6 to <12 years of age and Cohort 3: 4 weeks to <2 years, aiming to enroll 12 evaluable children for PK and safety in each cohort. At enrollment children start 3 ARVs, including chewable RAL formulation at 12 mg/kg/dose twice daily (twice the recommended pediatric dose). Intensive RAL PK sampling is done 1 week after ARV therapy is initiated and then a 4th ARV is added. Clinical and lab assessments are routinely completed. RAL is stopped at TB treatment completion and children are followed for additional 3 mos. PK targets are a geometric mean (GM) AUC12h of 14-45 (µM-h) and GM C12h ≥75 nM. Here we report the results from Cohort 1. Results: Among 12 children, 7 (58%) were male, median age 3 years (IQR 2-5), baseline Log10 RNA median 4.91 (IQR 4.42-5.42), median CD4 count 559 cells/ mL (IQR 390-1185), median CD4 percent 15% (IQR 9-24). PK at Week 1 showed GM AUC12h (%CV) of 28.8 mMxh (50%); the GM C12h was 229 nM (76%). 1/12 (8%with 95% CI [0%,34%]) had a grade 3 elevation of ALT at Week 4 deemed possibly related to RAL. RAL/ART were temporarily withheld for 21 days and then restarted, with no subsequent recurrence. While RAL was held temporarily, this child did not achieve virologic success (>1 log 10 drop from baseline at Week 8 or HIV RNA ≤400 copies/mL). 11/12 (92%), were virologically suppressed by Week 8, with 95% CI (62%, 100%). For n=12 at Week 8, median log 10 RNA change from baseline was -3.16 (IQR -3.79, -2.55), median CD4 change from baseline was 101 cells/mL (IQR -70 to 230], median CD4 percent change from baseline was 6.1% (IQR 1.9-9.7). Conclusion: A 12mg/kg dose twice daily of the oral chewable formulation of RAL safely achieved PK targets in HIV-infected children 2 to <6 years with TB.

844 BICTEGRAVIR/FTC/TAF SINGLE-TABLET-REGIMEN IN ADOLESCENTS: WEEK 24 RESULTS Aditya Gaur 1 , Carina Rodriguez 2 , Eric J. McGrath 3 , Elizabeth Hellstrom 4 , Afaaf Liberty 5 , Eva Natukunda 6 , Pope Kosalaraksa 7 , Kulkanya Chokephaibulkit 8 , Amy Coluci 9 , Sophia R. Majeed 9 , Danielle Porter 9 , Pamela Wong 9 , Erin Quirk 9 , Hiba Graham 9 , Cheryl Pikora 9 1 St. Jude Children’s Research Hospital, Memphis, TN, USA, 2 University of South Florida, Tampa, FL, USA, 3 Children’s Hospital of Michigan, Detroit, MI, USA, 4 Be Part Yoluntu Centre, Paarl, South Africa, 5 Chris Hani Baragwanath Hospital, Johannesburg, South Africa, 6 Joint Clinical Research Centre, Kampala, Uganda, 7 Khon Kaen University, Khon Kaen, Thailand, 8 Mahidol University, Bangkok, Thailand, 9 Gilead Sciences, Inc, Foster City, CA, USA Background: Bictegravir (BIC), a novel, unboosted integrase strand transfer inhibitor (INSTI) with a high genetic barrier to resistance, has been coformulated with emtricitabine and tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) into a once daily, single-tablet regimen (STR) of small tablet size that can be taken with/without food. We report pharmacokinetics (PK), safety and efficacy from a planned interim analysis of the first clinical trial of B/F/TAF in HIV-infected adolescents. Methods: Virologically suppressed adolescents (12 to <18 yrs) weighing ≥35 kg with HIV-1 RNA <50 c/mL for ≥6 months before screening and CD4 ≤200 cells/μL received B/F/TAF once daily in a prospective, 48-week (W), single-arm, open-label trial. Steady-state PK parameters in adolescents were compared to those observed in adults treated with B/F/TAF. Adverse events (AE), laboratory tests, and the proportion of subjects with HIV-1 RNA <50 c/mL were assessed through W24. Results: 24 adolescents enrolled; median age 15 yrs (range 12-17 yrs), median weight 48.9 kg (range 36.1-88.6 kg), 79% female, 52% Black, median CD4 count 708 cells/μL, 88% vertically infected. All (100%) had HIV-1 RNA <50 c/ mL at W24 and none met criteria for resistance testing. Mean change in CD4 count from baseline was 44 cells/μL. No clinically relevant differences in drug exposures of B/F/TAF components were observed compared with data from adults (Table). Through a median (Q1, Q3) duration of exposure to study drug of 25.6 (24.7, 26.6) weeks, the most common treatment emergent AE was upper respiratory tract infection (21%, 5 of 24); no other AE occurred in >2 participants. No subject discontinued for AE. All participants reported B/F/TAF size and shape to be acceptable, and mean (SD) adherence to study drug was high (97.1% [7.02]). µ µ Conclusion: The B/F/TAF STR maintained virologic suppression in all adolescent subjects enrolled and was well-tolerated through 24 weeks. Similar to adults treated with B/F/TAF, therapeutic plasma concentrations of all components of B/F/TAF were achieved. The efficacy and safety in adolescents is consistent with phase 3 B/F/TAF results in adults, which showed high

Poster Abstracts

CROI 2018 319