CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Therapeutic plasma concentrations of all components of E/C/F/TAF were achieved, consistent with potent antiviral activity of the regimen. Treatment was generally well-tolerated through 24 weeks with a favorable renal and bone safety profile. These promising findings support E/C/F/TAF’s eventual use in adolescents and its further evaluation in other pediatric populations. 954 Efficacy and Safety of Long-Term Tenofovir DF (TDF) Therapy in HIV-Infected Children Xavier Saez-Llorens 2 ; Jaime G. Deville 3 ; Ayesha Mirza 4 ; Janet S. Chen 5 ; Aditya Gaur 6 ; Mobeen Rathore 4 ; Dana Hardin 7 ;Ya-Pei Liu 1 ; Erin Quirk 1 GS-US-104-0352 StudyTeam 1 Gilead Sciences, Inc., Foster City, CA, US; 2 Hospital del Niño, Panama City, Panama; 3 University of California Los Angeles, Los Angeles, CA, US; 4 University of Florida, Jacksonville, FL, US; 5 Drexel University College of Medicine, Philadelphia, PA, US; 6 St Jude Children’s Research Hospital, Memphis, TN, US; 7 Eli Lilly, Indianapolis, IN, US Background: Limited long term data are available for pediatric TDF use. We describe preliminary efficacy and safety in HIV-infected children treated with TDF for up to 336 weeks. Methods: Children ages 2-16 years with HIV-1 RNA <400 copies/mL (c/mL) on a stavudine (d4T)- or zidovudine (ZDV)-containing regimen were randomized to maintain d4T or ZDV or switch to open label (OL) 8 mg/kg TDF oral powder or 300 mg tablets for 48 weeks. Following the randomized phase, subjects in the TDF arm could continue on TDF and those on d4T or ZDV could switch to OL TDF oral powder or tablets at investigator discretion. Subjects maintained their background ARVs for up to 336 weeks in three 96-week study extensions. Safety (adverse events [AE] and laboratories) and efficacy (HIV-1 RNA [Roche Amplicor or Taqman]) were assessed every 12 weeks. Spine and total body less head (TBLH) bone mineral density (BMD) was measured by dual energy X-ray absorptiometry every 24-48 weeks. Proportion with HIV-1 RNA < 50 copies/mL (missing=failure) was assessed. 95% CIs of the point estimate were calculated from the Exact method. Results: 89 subjects received TDF (49.4%male, median age 7 years, median CD4 1095 cells/mm 3 , median CD4% 34). Median TDF duration was 302 weeks. 79 subjects received TDF in OL extensions. Seven discontinued OL TDF for AEs (hypophosphatemia [n=2]; proteinuria [n=2]; brain neoplasm, glycosuria, and arthralgia and hypophosphatemia [n=1 each]). TDF adherence was 95% in 45/89 subjects (50.6%). At Week 336, 32/40 subjects (80.0%; 95% CI 64.4, 90.9%) had HIV-1 RNA <50 c/mL. The most frequent AEs were nasopharyngitis (62.9%), dental caries (23.6%), cough and diarrhea (both 21.3%), and gastroenteritis (20.2%). At Week 336, median change from BL in estimated GFR (Schwartz) was -28.7 mL/min/1.73m 2 (n = 38, BL 166.6 mL/min/1.73m 2 ) and median BMD percentage change from BL was +43.44% for spine (n=23) and +18.50% for TBLH (n=24). Overall 13/86 subjects (15.1%) had >4% decreases from BL in either spine or TBLH BMD, n=3 at >1 visit. Conclusions: Most HIV-1 infected children with data available maintained viral responses to TDF-based ARV at Week 336. TDF was well-tolerated. Estimated GFR changes were consistent with increases in age. Few TDF-recipients had persistent BMD decreases. TDF can be considered as a once-daily component of ARV therapy in HIV-infected children. 955 Acceptability of Lopinavir/r Minitabs, Tablets and Syrups in HIV-Infected Children Adeodata Kekitiinwa CHAPAS-2 Baylor College of Medicine Children’s Foundation Uganda, Kampala, Uganda Background: LPV/r ‘minitabs’ provided similar exposure to syrup in the CHAPAS-2 trial. After 12 weeks, they were more acceptable than syrups for young children, but older children preferred tablets. Here we describe acceptability at week 48. Methods: CHAPAS-2 was a randomised, 2-period crossover trial in HIV-infected infants/children taking first- or second-line ART with 2 NRTIs+LPV/r from 2 clinics (“JCRC”, “PIDC”) in Uganda. Infants aged 3-<12 months (group A, n=19) started syrup and switched at week 4 to minitabs; children aged 1-4 years (group B, n=26) started minitabs and switched to syrup or vice versa; and children aged 4-<13 years (group C, n=32) started tablets and switched to minitabs or vice versa. At week 8, all groups chose which formulation to continue. Formulation acceptability data were collected at weeks 4, 8, 12, and 48. VL was measured at week 48. Results: For groups A and B overall, the proportion preferring minitabs increased between weeks 0 and 12 and decreased at week 48 (group A 37%, 72%, 44%; group B 12%, 64% and 36% respectively). However at week 48, group B’s preferences differed between JCRC and PIDC: 70% JCRC vs 13% PIDC preferred minitabs. For older children (group C), minitabs were progressively less preferred to tablets over time: 41%, 19%, 13% at weeks 0, 12, 48 respectively. Formulations taken in the preceding 4 weeks reflected preferences; clinics differed: groups A/B at JCRC more likely to be on minitabs at week 48 (40%/82% JCRC vs 15%/20% PIDC respectively). For group C, 23% and 13%were on minitabs at weeks 12 and 48 respectively. Unpleasant taste was similarly reported among young children taking minitabs and syrups (37%/43% group A and 29%/26% group B), whereas among older children, minitabs were worse than tablets (40%/2%). There were no reported problems with storage and transportation for minitabs (0%/0% respectively) unlike syrups (23%/13%). Of 19 children with VL assayed at week 48, 14 were <50 c/ml and all were <1000 c/ml. Conclusions: For infants and young children, minitabs were more acceptable at week 12 but not at week 48. Differences between clinics could reflect bias among healthcare workers for different formulations. Minitabs taste similar to the syrup, are easier to store and transport than syrup bottles, and represent an alternative formulation for young children unable to swallow tablets. Improvements in taste of the current formulation may help sustain acceptability. 956 Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line ART Linda Aurpibul 1 ;Wasana Prasitsuebsai 2 ;Tavitiya Sudjaritruk 3 ; Pope Kosalaraksa 4 ; Nia Kurniati 6 ; Khanh HuuTruong 5 ;Viet Chau Do 7 ; SirinyaTeeraananchai 2 ; Stephen J. Kerr 2 theTASER-Pediatrics Study Group 1 Research Institute for Health Sciences, Chaing Mai University, Chiang Mai, Thailand; 2 The HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; 3 Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 4 Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand; 5 Children’s Hospital 1, Ho Chi Minh City, Viet Nam; 6 Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; 7 Children’s Hospital 2, Ho Chi Minh City, Viet Nam Background: Failure rates of second-line boosted protease inhibitor (PI) regimens in children in resource-limited settings are expected to rise over time. Therapeutic drug monitoring can contribute to assessments of adherence and inform decisions to conduct resistance testing. We assessed the performance characteristics of the US DHHS-

Poster Abstracts

569

CROI 2015