TUAB0102 - Oral Abstract
Rapid, robust and sustained antiviral response with once-daily (QD) dolutegravir (DTG, S/GSK1349572), a next generation integrase inhibitor (INI) in combination therapy in antiretroviral-naïve adults: 48 week results from SPRING-1 (ING112276)
Presented by Jan van Lunzen (Germany).
J. Van Lunzen1, F. Maggiolo2, B. Phung3, O. Tsybakova4, B. Young5,6, J. Gatell7, S. Almond8, M. St. Clair9, C. Brothers9, S. Min9
1University Medical Center, Hamburg-Eppendorf, Germany, 2Ospedali Riuniti de Bergamo, Bergamo, Italy, 3Hôpital Bichat-Claude Bernard, Paris, France, 4AIDS Center, Smolensk, Russian Federation, 5Rocky Mountain CARES/DIDC, Denver, United States, 6Health Connections International, Amsterdam, Netherlands, 7University of Barcelona, Barcelona, Spain, 8GlaxoSmithKline, Mississauga, Canada, 9GlaxoSmithKline, Research Triangle Park, United States
Background: DTG, has demonstrated potent antiviral activity with QD, unboosted dosing. SPRING-1 is an ongoing dose-ranging study from which the 50mg QD dose was selected for Phase III evaluation in INI-naïve subjects.
Methods: Multicentre, partially-blinded Phase IIb study in therapy-naïve adults receiving 10mg, 25mg or 50mg DTG or efavirenz (EFV) 600mg QD with TDF/FTC or ABC/3TC.
Results: 205 subjects received study drug. Plasma HIV-1 RNA declined faster across DTG doses vs. EFV; subjects maintained their responses to Week 48. A trend for higher CD4+ cell increases was observed across DTG arms vs EFV (+231 vs +174 cells/mm3; p=0.076). Response rates using superlow assay (< 2c/mL) are also shown. Four subjects across the DTG and EFV arms met protocol-defined virologic failure criteria; two continue on study after virologic re-suppression. No integrase-associated mutations have been observed to date. No new safety issues occurred to Week 48. Fewer grade 2-4 drug-related AEs were reported on DTG (8%) than EFV (20%); 6 subjects (2 on DTG; 4 on EFV) withdrew due to AEs. The most frequent events were gastrointestinal (2% vs 4%, DTG vs, EFV respectively), metabolic (3% vs 0%), psychiatric (0% vs 6%) and rash (0% vs 4%). No SAE was considered related to DTG. Mean change in LDL cholesterol was +0.55mg/dL and +15.88mg/dL among DTG and EFV subjects, respectively.
Conclusion: Once-daily, unboosted DTG was well-tolerated with little impact on lipids. DTG's rapid and robust potency was further substantiated using a highly sensitive assay for HIV RNA. Based on these results, Phase III studies are underway.
|Planned Week 48 Interim Analysis Results||DTG 10 mg (n=53)||DTG
25 mg (n=51)||DTG
50 mg (n=51)||EFV control (n=50)|
|Mean baseline HIV-1 RNA (log10 copies/mL)||4.42||4.38||4.58||4.46|
|%<50c/mL at 16, 24 and 48 wks (by TLOVR)||96%, 96%, 91%||90%, 90%, 88%||92%, 92%, 90%||58%, 82%, 82%|
|%<2c/mL at 16, 24 and 48 wks||n/d||n/d||49%, 67%, 53%||36%, 48%, 60%|
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