CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

950 Use of Maraviroc in HIV-1-Infected Paediatric Patients in Clinical Practice Claudia Palladino 1 ; Maria Luisa Navarro Gomez 6 ; Pere Soler-Palacín 5 ; Maria Isabel Gonzalez-Tome 7 ; Santiago Jimenez de Ory 6 ; Maria Espiau 5 ; Juan Antonio León-Leal 4 ; Clàudia Fortuny 3 ;Verónica Briz 2 CoRISpe working group 1 University of Lisbon, Lisbon, Portugal; 2 National Center for Microbiology, Madrid, Spain; 3 Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; 4 Hospital Infantil Universitario Virgen del Rocío, Seville, Spain; 5 Hospital Universitari Vall d’Hebron, Barcelona, Spain; 6 Hospital General Universitario Gregorio Marañón, Madrid, Spain; 7 Hospital Universitario Doce de Octubre, Madrid, Spain Background: Maraviroc (MVC) is the first CCR5-antagonist approved in 2007 in HIV-infected adult patients with CCR5-tropism, while it is still under evaluation in paediatric patients. Our aimwas to evaluate the effectiveness, safety and tolerability of MVC-based salvage therapy outside clinical trials in HIV-1-vertically infected paediatric patients. Methods: A multicenter retrospective study of 20 treatment-experienced children (n=6) and adolescents (n=14) followed at least for 20 weeks was performed. Immunological, virological and clinical status of patients at baseline and during follow-up was analyzed every 3-6 months. Individuals were monitored from baseline (i.e., the date of MVC initiation) until the administrative censoring date or MVC discontinuation if occurred. Results: At baseline, median viral load (VL) and CD4+T-cell (CD4 count) were 3.8 log and 672 (25%) cells/ μ l (IQR:231–836) and 4.1 log and 315 (22%) cells/ μ l (IQR:175–657) in children and adolescents, respectively without significant differences. Patients mainly harboured an HIV-1 subtype B virus (85%) with confirmed CCR5 tropism. All patients but one presented extensive resistance profile with 10 (53%) patients showing triple drug class resistance mutations (NRTI/NNRTI/PI). At least 1 fully active drug was prescribed to 18 (95%) patients as backbone regimen, of whom 17 (85%) received MVC with one or more new drugs (DRV/r; ETR; RLT). Median follow-up with MVC was 116 weeks (IQR:25–198). Sixteen out of twenty (80%) patients reached undetectable VL [(median at 13 weeks, (5–35)] with a median decrease in VL from baseline of 1.7 log. Twelve out of sixteen (75%) maintained virological suppression for a median of 105 weeks (IQR:44–208) of which 9/12 (45%) patients maintained uVL until the end of the follow-up for a median of 132 (50-230) weeks. Immunological recovery was observed in 14/20 patients with median increase of 275 cells/ μ l (IQR:135–500). No adverse events related to MVC-based therapy were reported. MVC interruption was observed in 8 patients, because of virologic failure (n=4); simplification (n=3); poor adherence (n=1). Two patients experienced emergence of CXCR4 variants and one of dual/mixed variants. Laboratory abnormalities included ALT/AST elevation (n=7), hypercholesterolemia (n=9), hypertriglyceridemia (n=12). Conclusions: MVC is useful as a salvage therapy in children and adolescents with extensive resitance profile leading to maintained virological suppression in up to 60% of our cohort patients. 951 Safety and Pharmacokinetics of Elvitegravir in HIV-1 Infected Pediatric Subjects Joseph M. Custodio 1 ;Victor Musiime 2 ; Aditya Gaur 3 ; Elizabeth McFarland 4 ;Wasana Prasitsuebsai 5 ; Lize Hellstrom 6 ; XuelianWei 1 ; Rebecca Begley 1 ; Srinivasan Ramanathan 1 ; Sean R. Bennett 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 University of Colorado Denver, Aurora, CO, US; 5 HIV - NAT, Bangkok, Thailand; 6 Be Part Yoluntu Centre, Cape Town, South Africa Background: Safe and effective pediatric antiretroviral therapies are needed. Elvitegravir (EVG), a once-daily integrase inhibitor, is indicated in treatment-experienced HIV-1 infected adults when administered with a ritonavir (r)-boosted protease inhibitor (PI/r). The safety and pharmacokinetics (PK) of EVG were evaluated in a completed lead-in phase of a study in 6 to <11 year old HIV-infected subjects upon addition to a PI/r-containing background regimen consisting of at least 2 fully-active agents. Methods: Treatment-experienced subjects 6 to <11 years of age, weighing ≥ 17 kg with suppressed viremia (HIV-1 <50 c/mL) or failing a current antiretroviral regimen (HIV-1 RNA >1,000 c/mL) received EVG (adult or pediatric formulation) once daily in addition to their background regimen including either lopinavir/r or atazanavir/r. The adult EVG dose (85 mg) was administered in subjects >30 kg and reduced to 50 mg in subjects ≥ 17 kg to <30 kg. Intensive PK was performed on or after Day 10 (steady state). EVG exposure (primarily AUC tau ) was compared to exposures in adults from EVG+PI/r Phase 3 trials by an analysis of variance using a mixed-effects model for parallel group design. Adverse events (AE) and routine laboratory tests were assessed. Results: A total of 14 subjects (57%male, 14% Asian, 71% black and 14%white) were enrolled with a median age of 10 years (range: 6-11) and a median weight of 26 kg (range: 18-47). At baseline, mean CD4 count was 811 cells/ m L; 13 of 14 subjects had HIV RNA <50 c/mL. There were no deaths or AEs leading to premature study drug discontinuation. No EVG-related SAEs were observed. No AE occurred in more than one subject. EVG PK is summarized in Table 1. The geometric mean ratio (GMR) of EVG AUC tau , C max , and C trough was 136%, 147%, and 129%, respectively, versus adult exposure. Importantly, mean EVG C tau was ~11-fold above the in vitro protein-binding adjusted IC 95 (44.5 ng/mL). Moreover, subjects >30 kg or ≥ 17 kg to <30 kg (receiving EVG 85 or 50 mg, respectively) showed EVG exposure associated with safety and efficacy based on extensive PK-pharmacodynamic analyses in adults. These study data are consistent with EVG PK in children >12 years of age.

Poster Abstracts

Conclusions: Administration of EVG once daily with a PI/r in children 6 to <11 years old provides therapeutic EVG exposure with mean trough concentrations ~11-fold above IC 95 and appears well tolerated. These results support continued evaluation of the efficacy and safety of EVG in pediatric populations.

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CROI 2015