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

of results 205 subjects received study drug: 86% male, 20% nonwhite, 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 (<1log10 decline by Week 4), and 2 on S/GSK1349572 (Week 4 and 24 rebound >400c/mL with no INI mutation detected). No dose-related clinical or laboratory toxicities were observed. More drugrelated 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