Once-daily S/GSK1349572 combination therapy in antiretroviral-naïve adults: rapid and potent 24-week antiviral responses in SPRING-1 (ING112276)

Abstract

Purpose of study: S/GSK1349572, a next-generation HIV-1 integrase inhibitor, has previously demonstrated potent antiviral activity in Phase 2a with once-daily, unboosted dosing. SPRING-1 is an ongoing dose-ranging study designed to select a dose to for Phase 3 evaluation. Methods: SPRING-1 is a Phase 2b, multicentre, partially-blinded study in therapy-naive adults, randomized 1:1:1:1 to 10mg, 25mg or 50mg of S/GSK1349572 or efavirenz(EFV) 600mg once-daily with either co-formulated TDF/FTC or ABC/3TC. Summary of results: 205 subjects received study drug: 86% male, 20% non-white, 26%>100,000c/mL HIV-1 RNA, 67% TDF/FTC. Plasma HIV-1 RNA declined rapidly across all S/GSK1349572 doses with no differences in NRTI subgroups. Three protocol-defined virologic failures occurred, 1 on EFV ( 400c/mL with no INI mutation detected). No dose-related clinical or laboratory toxicities were observed. More drug-related AEs of moderate-or-higher intensity were reported on EFV (20%) than S/GSK1349572 (6%) arms; none occurred in more than 1 S/GSK1349572 subject. The most frequent category of such events reported by subjects receiving EFV and S/GSK1349572 were gastrointestinal (4% vs. 2%, respectively); other frequent events on EFV were psychiatric (6%) and rash (4%) disorders. No SAE was considered related to S/GSK1349572. Six subjects (2: S/GSK1349572 and 4: EFV) withdrew due to AEs. Mean change from baseline in LDL cholesterol was +0.023mmol/L among S/GSK1349572 subjects and +0.468mmol/L among EFV subjects. S/GSK1349572 demonstrated low pharmacokinetic variability and drug exposure increased with dose. Table ​1 Conclusions: S/GSK1349572 administered once-daily without a PK booster was well tolerated with potent antiviral activity at all doses explored in SPRING-1. The greater CD4+ cell increases on S/GSK1349572 merit further observation and confirmation. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-O50 Cite this article as: Rockstroh et al.: Once-daily S/GSK1349572 combination therapy in antiretroviral-naive adults: rapid and potent 24- week antiviral responses in SPRING-1 (ING112276). Journal of the International AIDS Society 2010 13(Suppl 4):O50. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112866/