CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Figure: Mean adult HIV incidence over 10 years of implementation in each model scenario

South Africa

Uganda

2.52 (2.33-2.72)

1.12 (0.98-1.26)

1.00 (0.92-1.26)

0.56 (0.50-0.62)

0.68 (0.54-0.82)

0.35 (0.30-0.39)

HIV incidence (cases per 100 person-years)

0.00 0.50 1.00 1.50 2.00 2.50 3.00 0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10

Years since start of intervention

Current Practice

Home HTC

ART for SDC

Bars represent 95% confidence intervals

1120 Pharmacokinetics, Safety, and Efficacy of Maraviroc in Pediatric Patients With R5 HIV Carlo Giaquinto 1 ; Muthuhadini P. Mawela 2 ; Kulkanya Chokephaibulkit 3 ; Annie Fang 4 ; Elna van der Ryst 5 ; Srinivas RaoValluri 4 ; ManoliVourvahis 4 ; Rebecca Zhang-Roper 6 ; Lynn McFadyen 7 ; Jayvant Heera 8 1 Univ of Padova, Padova, Italy; 2 Sefako Makgatho Hlth Scis Univ, Pretoria, South Africa; 3 Siriraj Hosp, Mahidol Univ, Bangkok, Thailand; 4 Pfizer, Inc, New York, NY, USA; 5 Pfizer Inc, The Rsr Network, Sandwich, UK; 6 GSK, Stockley Park, UK; 7 Pfizer, Inc, Sandwich, UK; 8 Pfizer, Inc, Groton, CT, USA Background: Maraviroc (MVC) is a CCR5 antagonist approved to treat adults infected with CCR5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics (PK), safety and efficacy of MVC in treatment-experienced (TE) pediatric patients. Methods: This is an open-label, two-stage (stage 1: dose-finding; stage 2: safety/efficacy), age-stratified, non-comparative, multicenter study to evaluate the PK, safety and efficacy of MVC plus optimized background therapy (OBT) in TE children infected with R5 HIV-1. A total of 103 participants were enrolled into one of four age/formulation cohorts (Table) and dosed twice daily. Initial doses were determined by body surface area (BSA) and OBT, based on interactions with MVC in adults. Dose adjustment and PK re-evaluation occurred if average concentrations (C avg ) at Week 2 were <100 ng/mL (stage 1). Results: The majority of participants (90/103) included in the Week 48 primary analysis received OBT containing potent CYP3A4 inhibitors. The dosing strategy resulted in 49/50 stage 1 participants rolling over into stage 2 achieving C avg concentrations ≥100 ng/mL irrespective of age, BSA or OBT, and an exposure range similar to that seen in adults. MVC was well-tolerated with a safety profile comparable to that of adults. The majority of treatment-emergent adverse events (TEAEs) were of Grade 1 severity. There were no deaths. None of the Grade 3 or 4 TEAEs or serious adverse events was considered to be related to MVC. Fourteen subjects had Grade 3 or 4 laboratory abnormalities with Grade 3 neutropenia the most common (n=8). All cohorts had a median decrease from baseline in HIV-1 RNA of >1 log 10 , while 67/103 subjects (65.0%) achieved HIV-1 RNA <400 copies/ mL using the FDA snapshot (MSDF) algorithm, and 49/103 (47.5%) achieved HIV-1 RNA <48 copies/ml. An increase from baseline in median CD4+ cell count and percentage was seen for all age-groups. A total of 23 (22.3%) patients experienced protocol-defined virologic failure with few instances of non-R5 tropism (n=5), MVC resistance (n=1) or clinically , with exposure ranges similar to that observed in adults. MVC’s safety profile in this population was comparable to that seen in adults with no new safety concerns identified. Virologic efficacy was comparable to what was reported in a similarly treatment-experienced adult population. These data support dosing recommendations for TE patients 2-<18 years old. relevant resistance-associated mutations (n=3). Conclusions: Participants achieved the target C avg

Poster Abstracts

457

CROI 2016