IAS 2011 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)

TUAB0102 - Oral Abstract Session

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. Young^5,6, 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%

[SPRING-1 Results]