CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

952 Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs Danielle P. Porter ; Sean R. Bennett; Erin Quirk; Michael D. Miller; Kirsten L.White Gilead Sciences, Inc., Foster City, CA, US

Background: GS-US-236-0112 and GS-US-292-0106 are international, ongoing, phase 2/3, open-label, single arm, 48-week studies evaluating the safety and efficacy of the integrase inhibitor-based single-tablet regimens (STRs) elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) in HIV-1 infected treatment-naïve adolescents. Here, we present resistance results from a planned Week 24 interim analysis. Methods: Genotypic analyses of HIV-1 protease (PR), reverse transcriptase (RT) and integrase (IN; GS-US-292-0106 only) were performed at screening for both studies. Subjects with resistance to study drugs were excluded. Subjects in the postbaseline resistance analysis population (subjects with HIV-1 RNA ≥ 400 copies/mL at virologic failure) had genotypic/phenotypic analyses at failure for PR, RT, and IN. Results: The Week 24 interim analysis included 21 subjects on E/C/F/TDF and 23 subjects on E/C/F/TAF. Most subjects on E/C/F/TDF had HIV1 subtype C (47.6%, 10/21) or B (38.1%, 8/21) with subtype AE also present (14.3%, 3/21). Most subjects on E/C/F/TAF had HIV1 subtype A1 (56.5%, 13/23) with the remainder having subtype AE (17.4%, 4/23), B (17.4%, 4/23), D (4.3%, 1/23), or complex mixtures (4.3%, 1/23). HIV-1 subtype distribution correlated with geography (A1, Uganda; AE, Thailand; B, USA; C, South Africa). Resistance mutations detected at baseline (not excluded at screening) are shown in Table 1. At Week 24, 85.7% (18/21) of subjects on E/C/F/TDF and 91.3% (21/23) on E/C/F/TAF had virologic success (HIV-1 RNA <50 c/mL) by FDA snapshot. Virologic response rates were similar across subtypes. Enrolled subjects with pre-existing IN-, NNRTI-, NRTI-, and PI-associated resistance mutations had virologic response rates similar to the overall study population (Table 1). One subject on E/C/F/TDF (4.8%, 1/21) and no subjects on E/C/F/TAF (0/23) met the criteria for postbaseline resistance analysis; no emergent resistance was detected. No subjects in either study experienced suboptimal virologic response.

Conclusions: In this Week 24 interim analysis of two clinical trials in treatment-naïve adolescents, the E/C/F/TDF and E/C/F/TAF STRs demonstrated efficacy against diverse HIV-1 subtypes with no emergent resistance. E/C/F/TDF and E/C/F/TAF are potentially effective treatment options for HIV-infected adolescent populations globally. 953 Week-24 Data From a Phase 3 Clinical Trial of E/C/F/TAF in HIV-Infected Adolescents Hilda Kizito 2 ; Aditya Gaur 3 ;Wasana Prasitsuebsai 4 ; Natella Rakhmanina 5 ; Eileen Lawson 1 ;Yongwu Shao 1 ; Sean R. Bennett 1 ; Andrew Cheng 1 ; Erin Quirk 1 1 Gilead Sciences, Inc., Foster City, CA, US; 2 Joint Clinical Research Centre, Kampala, Uganda; 3 St Jude Children’s Research Hospital, Memphis, TN, US; 4 HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand; 5 Children’s National Health System, Washington, DC, US Background: EVG/COBI/FTC/tenofovir alafenamide (TAF) [E/C/F/TAF] is an integrase inhibitor-based single tablet regimen in clinical development for use in HIV-infected adolescents. Pharmacokinetics, safety and efficacy from a planned interim analysis of the first clinical trial of E/C/F/TAF in adolescents are reported. Methods: Treatment-naïve 12 to <18 year-olds weighing ≥ 35 kg with HIV-1 RNA >1000 copies/mL (c/mL), CD4 >100 cells/ μ L and eGFR>90 mL/min/1.73m 2 received E/C/F/ TAF once daily in a prospective, 2-part, 48-week, single-arm, open-label trial. Steady-state pharmacokinetic (PK) parameters were compared to an adult reference population by ANOVA, and related to the range of exposures associated with antiviral activity in adults. Adverse events (AE), laboratory tests, and the proportion of subjects with HIV-1 RNA < 50 c/mL were assessed through Week 24. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: The trial enrolled 48 adolescents with a median age of 15 years, median weight of 52 kg, 58% female, 88% Black, 13% Asian, 67% vertically infected, 35%with HIV-1 RNA > 100,000 c/mL, median CD4 count 468 cells/ μ L, and median serum creatinine [sCr] 0.57 mg/dL. TAF, TFV, EVG, COBI, and FTC PK profiles of adolescents were consistent with those in adults. Of 23 subjects followed to Week 24, 21 (91%) had HIV-1 RNA <50 c/mL (Figure). No deaths or AE-related discontinuations occurred. The most frequent AEs were nausea (23%), upper respiratory infection (21%), and diarrhea (17%). One serious AE of visual impairment and intermediate uveitis occurred and resolved without interruption of E/C/F/ TAF. The median change in sCr was +0.08 mg/dL at Week 24, consistent with cobicistat’s inhibition of renal tubular Cr secretion. No renal failure or proximal renal tubulopathy occurred. From baseline to Week 24, the change in median spine BMD was +2.8%with a change in height-adjusted (HA) Z-score of +0.02 and 2/23 subjects (9%) having a decrease of ≥ 4%. The change in median total body less head BMD was +0.3%with a change in HA Z-score of +0.09 and no decreases of ≥ 4%. No fractures occurred.

Poster Abstracts

568

CROI 2015