|Once-daily Oral GSK1265744 (GSK744) as Part of Combination Therapy in Antiretroviral Naïve Adults: 24-week Safety and Efficacy Results from the LATTE Study (LAI116482)|| |
|D. Margolis1, L. Bhatti2, G. Smith3, W. Weinberg4, C. Brinson5, T. Mills6, E. Dejesus7, B. Stancil1, P. Wannamaker1, M. Bomar1, M. St Clair1, W. Spreen1, J. Goodrich8|
|1GSK, RTP, United States, 2AIDS Healthcare Foundation, Beverly Hills, United States, 3Maple Leaf Medical Clinic, Toronto, Canada, 4Kaiser Permanente, Atlanta, United States, 5Central Texas Clinical Research, Austin, United States, 6HIV Clinic, Los Angeles, United States, 7Orlando Immunology Center, Orlando, United States, 8ViiV Healthcare, RTP, United States|
|Objective: Evaluate safety, efficacy and tolerability of the HIV-1 integrase inhibitor, GSK744, and to select a dose for further evaluation.|
Methods: LATTE is a Phase 2b, multicentre, partially-blinded dose-ranging study in therapy-naïve adults, randomized 1:1:1:1 to the induction regimen GSK744 10mg, 30mg or 60mg or efavirenz (EFV) 600mg once-daily with TDF/FTC or ABC/3TC through 24 weeks, followed by a two drug maintenance regimen of GSK744 plus rilpivirine 25mg through 96 weeks (ongoing).
Results: 243 subjects received drug: 96% male, 38% non-white, 16%>100,000c/mL HIV-1 RNA, 61% TDF/FTC. Plasma HIV-1 RNA declined rapidly across all GSK744 doses with no differences by NRTI. Time to HIV RNA < 50c/mL was shorter in GSK744 arms than EFV arm, 76% vs 24% at Week 4 respectively; (each p< 0.001 vs. EFV; log-rank test). Six virologic failures occurred without evolution of resistance, one with each GSK744 dose, three on EFV. Drug-related AEs of ≥ Grade 2 were reported by 13% and 16% of GSK744 and EFV recipients, respectively. Six SAEs occurred on GSK744 (none related); three SAEs on EFV (one related - suicide attempt). Twelve subjects (4:GSK744 and 8:EFV) withdrew due to AEs. Rates of any graded ALT elevations were 15% on GSK744 and 19% on EFV; two subjects on GSK744 60mg with pre-existing steatohepatitis developed asymptomatic Grade 4 ALT elevations with normal bilirubin levels at W4 and W8, which resolved off drug.
| ||GSK744 10 mg (n=60)||GSK744 30 mg (n=60)||GSK744 60 mg (n=61)||EFV control
|Mean baseline HIV-1 RNA
|Mean change from baseline HIV-1 RNA at 2 weeks (log10c/mL)||-2.53||-2.31||-2.50||-1.88|
|%<50c/mL at 24 wks by Snapshot
(95% CI)||53 (88%)
(80%, 96%)||51 (85%)
(76%, 94%)||53 (87%)
(78%, 95%)||46 (74%)
|Median baseline (change from baseline at 24 weeks) CD4+ cells/mm3||415
[Week 24 Interim Analysis Results (Planned)]Conclusion:
Oral GSK744 administered once-daily with NRTIs was generally safe and well tolerated with antiviral activity at all doses through 24 Weeks. Time to undetectable viral load was significantly shorter in the GSK744 arms. Subjects with a HIV-1 VL < 50 c/ml prior to Week 24 transitioned to GSK744 + rilpivirine or remained on EFV + NRTIs through 96 weeks. These data support progression of GSK744 as an oral and long acting agent for HIV treatment.
David Margolis , GSK , RTP , United States
Assigned in sessions:
18.10.2013, 10:30-12:30, Parallel Session, PS7, Antiretroviral Therapy II, Bozar (Plenary Hall)