Abstract Body

Background: GSK1265744 (744) is an HIV integrase inhibitor (INI) under development as both an oral tablet and long-acting (LA) injectable. LATTE was designed to select an oral dose of 744 and to evaluate a two drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy. A separate study to evaluate 744 LA + RPV LA is planned.

Methodology: Phase 2b, multicentre, partially-blinded dose-ranging study in ART-naive HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral 744 10 mg, 30 mg, 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through W24, followed by a two drug oral maintenance regimen of 744 + RPV 25 mg through W96 (ongoing).

Results: 243 patients (Pts) were randomized and treated (ITT-E): 96% male, 38% non-white, 16%>100,000 c/mL HIV-1 RNA, 61% TDF/FTC. Plasma HIV-1 RNA declined rapidly across all 744 doses with no differences by NRTI. 744 Pts with a VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg; no change was made to the EFV arm. 207 Pts were treated in the ITT-Maintenance Exposed (ITT-ME) population. At W48, 82% of 744 + RPV Pts and 71% of EFV Pts were <50 c/mL by Snapshot (ITT-E). Amongst Pts who began 744 + RPV at W24, 93% were <50 c/mL by Snapshot at W48 (ITT-ME), with similar response rates for all 744 doses. Three virologic failures occurred during Maintenance (744 10 mg, 744 30 mg , EFV). One Pt on 744 10 mg + RPV, with very low 744 and RPV drug exposures, developed virologic failure at W48 with treatment-emergent INI (Q148R) and NNRTI (E138Q) resistance mutations. Drug-related AEs ≥ Grade 2 were reported by 14% and 19% of 744 and EFV Pts, respectively. Drug-related AEs ≥ Grade 2 during Maintenance were uncommon, 744 (4%) and EFV (4%). SAEs occurred in eleven 744 Pts (none related); and three EFV Pts (one related – suicide attempt). Fewer 744 Pts withdrew due to AEs (3%), than EFV Pts (13%). Treatment emergent max lab abnormalities ≥ Grade 3 occurred in 21% (744) and 31% (EFV) of Pts through W48. Rates of any graded ALT elevations were 17% (744) and 21% (EFV).

Conclusions: Oral 744 + NRTIs was well tolerated with good antiviral activity at all doses through W24. When used as maintenance therapy in virologicall suppressed Pts, the two drug regimen 744 + RPV provided similar antiviral activity to EFV+NRTIs through the W48 primary analysis. 744 + RPV was safe and well tolerated across all 744 doses. These data support further development of 744 and the planned evaluation of 744 LA + RPV LA as an injectable regimen for HIV treatment.