CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

and 13 (29%) 2 NRTIs (9 TDF/FTC, 3 ABC/3TC, 1 ABC + TDF). In the primary endpoint, 41/45 (91.1%, Exp) and 44/45 (97.8%, Ctrol) had VL<50 c/mL at 48 weeks (dif 6.7%; 95%CI: -17.4, 4.1). In an analysis allowing NRTI reintroduction, rates of VL <50 c/mL at 48 weeks were 95.6% (Exp) and 97.8% (Ctrol) (dif -2.2% 95%CI: -7.2, 2.7). CD4 cell counts remained stable in both arms. One subject developed VF (confirmed VL>200 c/mL, Exp). New resistance mutations were not selected in genotypic resistance tests. There were 10 grade 3/4 adverse events, 5 in each arm (none related to study drugs). There was one death (lung neoplasia, Exp Arm ). Conclusions: In multitreated patients receiving a successful salvage regimen with at least 2 active drugs (one a boosted PI), the withdrawal of NRTIs without complete activity was safe and associated with high rates of continued virologic suppression at 48 weeks. 554LB Cabotegravir and Rilpivirine As 2-Drug Oral Maintenance Therapy: LATTE W96 Results David A. Margolis 1 ; Cynthia C. Brinson 2 ; Graham H. Smith 3 ; Jerome deVente 4 ; Debbie P. Hagins 5 ; Sandy K. Griffith 1 ; Marty H. St. Clair 1 ; KimberlyY. Smith 6 ; Peter E.Williams 7 ;William R. Spreen 1 1 GlaxoSmithKline, Durham, NC, US; 2 Central Texas Clinical Research, Austin, TX, US; 3 Maple Leaf Medical Clinic, Toronto, Canada; 4 Living Hope Foundation, Long Beach, CA, US; 5 Chatham County Health Department, Savannah, GA, US; 6 ViiV Healthcare, Durham, NC, US; 7 Janssen Pharmaceuticals, Inc, Beerse, Belgium Background: Cabotegravir (CAB, GSK744) is an HIV INSTI under development as both an oral and long-acting (LA) injectable. LATTE was designed to select an oral dose of CAB and to evaluate a two-drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy. Methods: Phase 2b, multicentre, partially-blinded, dose-ranging study in ART-naïve HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral CAB 10 mg, 30 mg, 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through Week (W) 24, followed by a two-drug oral maintenance regimen of CAB (blinded dose) + RPV 25 mg through W96. CAB patients (pts) with a VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg; no change was made for EFV + NRTIs pts (ITT- Maintenance Exposed (ME)). Results: 243 pts were randomized and treated (ITT-E): 96%male, 38% non-white, 14%>100,000 c/mL HIV-1 RNA, 61% TDF/FTC. Amongst pts who began CAB + RPV at W24, 86% had HIV-1 RNA <50 c/mL by snapshot at W96 overall, relative to 83% of pts continuing EFV (ITT-ME). Five protocol-defined virologic failures occurred during 72 weeks of Maintenance (CAB 10 mg [2], CAB 30 mg [1], EFV [2] including two on CAB + RPV with treatment emergent resistance [INI + NNRTI, NNRTI]). Drug-related AEs ≥ Grade 2 were reported by 14% and 19% of CAB and EFV pts, respectively with 4% and 4% occurring during the 72WMaintenance phase. SAEs occurred in 10% of CAB pts (none drug related); and 6% EFV pts (one drug-related - suicide attempt). Fewer CAB pts withdrew due to AEs (3%), than EFV pts (15%), mostly prior to the Maintenance phase. Treatment-emergent lab abnormalities ≥ Grade 3 occurred in 26% of CAB and 37% of EFV pts through W96, most commonly elevated creatine kinase. Rates of any graded ALT elevations were 20%with CAB and 21%with EFV.

Poster Abstracts

Conclusions: When used as two-drug maintenance therapy in virologically suppressed pts, CAB + RPV provided similar antiviral activity to EFV+2 NRTIs through W96. CAB + RPV was well tolerated overall, with no SAEs considered drug related and few AEs leading to withdrawal. Considering all safety and efficacy data, oral CAB 30mg once-daily was selected for further development. Results support the selected dose regimens for the ongoing Ph2 LATTE-2 study with CAB LA + RPV LA as injectable two-drug maintenance therapy.

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CROI 2015