Presentation Abstract

Session: 073-New Antiretroviral Therapy: Bench to Bedside
Monday, Sep 10, 2012, 8:30 AM -11:00 AM
Presentation Title: H-556b - Dolutegravir (DTG; S/GSK1349572) + Abacavir/Lamivudine Once Daily Statistically Superior to Tenofovir/Emtricitabine/Efavirenz: 48-Week Results - SINGLE (ING114467)
Location: Room 104
Presentation Number: H-556b
Pres. Time: Monday, Sep 10, 2012, 10:30 AM -10:45 AM
Category: H2
Keywords: Dolutegravir; Abacavir/Lamivudine; treatment-nieve
Author(s): S. Walmsley, MD - Professor of Medicine1, A. Antela, MD - Doctor 2, N. Clumeck, MD - Professor 3, D. Duiculescu, MD - Doctor 4, A. Eberhard, MD - Doctor 5, F. Gutiérrez, MD - Doctor 6, L. Hocqueloux, MD - Doctor 7, F. Maggiolo, MD - Doctor 8, U. Sandkovsky, MD - Asst. Professor of Medicine 9, C. Granier, DESS - Mgr, Statistics 10, B. Wynne, MD - Physician Project Leader 10, K. Pappa, PharmD - Clinical Investigation Leader 10;
1Univ Hlth. Network, Toronto, Canada, 2Hosp. Clinico Univ, Santiago de Compostela, Spain, 3Ctr Hosp Univ Saint-Pierre, Brussels, Belgium, 4Infectious Tropical Diseases Hosp Dr. Victor Babes, Bucharest, Romania, 5MVZ Karlsplatz HIV Res/Clin Care Ctr, Munich, Germany, 6Hosp Univ de Elche, Alicante, Spain, 7Ctr Hosp Regional d’Orléans, Orléans, France, 8Antiviral Therapy Unit Ospedali Riuniti, Bergamo, Italy, 9Univ Nebraska Med Ctr, Omaha, NE, 10GlaxoSmith-Kline, RTP, NC.
Financial Disclosures:  S. Walmsley,
ViiV Role(s): Other, Advisory Board Consultant.
Abbott Role(s): Other, Advisory Board Consultant.
Merck Role(s): Other, Advisory Board Consultant.
Bristol-Myers Squibb Role(s): Other, Advisory Board Consultant.
Gilead Role(s): Other, Advisory Board Consultant.
Johnson & Johnson Role(s): Other, Advisory Board Consultant.
GlaxoSmith-Kline Role(s): Research Contractor.
A. Antela,
GlaxoSmith-Kline Role(s): Research Contractor.
N. Clumeck,
GlaxoSmith-Kline Role(s): Research Contractor.
D. Duiculescu,
GlaxoSmith-Kline Role(s): Research Contractor.
A. Eberhard,
GlaxoSmith-Kline Role(s): Research Contractor.
F. Gutiérrez,
Abbott Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Boehringer-Ingelheim Role(s): Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Bristol-Myers Squibb Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Gilead Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
GlaxoSmith-Kline Role(s): Research Contractor, Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Janssen-Cilag Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Merck Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
Pfizer Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
ViiV Role(s): Other, Research funding, consultancy fee,lector sponsorship or advisory board consultant.
L. Hocqueloux,
GlaxoSmith-Kline Role(s): Research Contractor.
F. Maggiolo,
GlaxoSmith-Kline Role(s): Research Contractor.
U. Sandkovsky,
GlaxoSmith-Kline Role(s): Research Contractor.
C. Granier,
GlaxoSmith-Kline Role(s): Employee.
B. Wynne,
GlaxoSmith-Kline Role(s): Employee.
K. Pappa,
GlaxoSmith-Kline Role(s): Employee.
Abstract: Background: Dolutegravir (DTG; S/GSK1349572), a once-daily, unboosted integrase inhibitor, has shown rapid & durable antiviral responses, with favorable tolerability. Methods: SINGLE, a double-blind, double-dummy, non-inferiority phase III study in therapy-naïve adults with HIV-1 RNA ≥1000 c/mL, randomized subjs to DTG 50 mg + ABC/3TC QD or TDF/FTC/EFV QD. Primary endpoint: proportion of subjs with HIV-1 RNA <50 c/mL at week 48 (FDA Snapshot, ITT-Exposed). Tolerability, safety, & viral resistance evaluated. Results: 833 enrolled (84% males; 32% non-white); groups similar at BL. At Week 48, 88% of DTG + ABC/3TC and 81% of TDF/FTC/EFV subjects had HIV-1 RNA <50 c/mL confirming non-inferiority. Using pre-specified testing procedure, statistical superiority was concluded (p=0.003). Both Time to Suppression and Change from BL in CD4 favored DTG arm and were significant. Protocol defined virological failure: 4% on each arm. No INI or NRTI resistance observed on DTG arm, vs. 1 NRTI RAM and 4 NNRTI RAMs on TDF/FTC/EFV. Conclusion: DTG + ABC/3TC was highly effective and better tolerated through 48 weeks than TDF/FTC/EFV single-tablet regimen.
SINGLE Week 48 Data
DTG+ABC/3TC
(N=414)		TDF/FC/EFV
(N=419)		Difference
[95% CI]
(P value)
Baseline Characteristics
Median CD4 cell count (cells/mm3)335339-
Median HIV RNA
(%>100k c/mL)		4.7 log (32%)4.7 log (31%)-
Efficacy Results
Proportion <50c/mL (SNAPSHOT)364 / 414 (88%)338 / 419 (81%)7.4%
[2.5, 12.3]
P=0.003
Proportion <50c/mL
(Per protocol)		90%81%8.7%
[3.9, 13.4]
Median time to <50c/mL and hazard ratio28 days84 days2.3
[2.0; 2.7]
P<0.0001
Change from BL in CD4 cells/mm326720859
[33, 84]
P<0.001
Safety Results
AEs Leading to withdrawal
by System Organ Class
(>2%, either arm)
Overall10 (2%)42 (10%)
Psychiatric disorders2 (<1%)15 (4%)
Nervous system disorders013 (3%)
Skin and subcutaneous
tissue disorders		2 (<1%)8 (2%)
Gastrointestinal disorders08 (2%)



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