Activity of the integrase inhibitor S/GSK1349572 in subjects with HIV exhibiting raltegravir resistance: week 24 results of the VIKING study (ING112961)

Background: S/GSK1349572(572) showed potent activity in Phase 2 studies in INI-naive HIV-infected subjects and limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. VIKING is an ongoing 24-week Phase 2b pilot study assessing 572 in subjects with RAL-resistant HIV. A good antiviral response during the functional monotherapy phase (through Day 11) of this pilot study was observed with a strong correlation between baseline susceptibility to 572 and response. Methods: 27 RAL-experienced, adult subjects, with screening plasma HIV-1 RNA ≥1000c/mL and genotypic resistance to RAL and ≥ 2 other ART classes, received 572 50mg QD in Cohort I while continuing their failing regimen (without RAL). At Day 11 the background regimen was optimised, where feasible, and 572 continued. The antiviral activity (primary end-point at Day 11), tolerability, safety and virology data through Week 24 of Cohort I are presented. A higher dose is being assessed. Results: At Baseline, subjects harboured viruses displaying high level resistance to RAL (median fold change in susceptibility [FC] 161, range: 0.57- >166) and low median FC to 572 (1.46, range: 0.55-35). Median (IQR) Baseline CD4+ and plasma HIV-1 RNA were 110 cells/mm3 (40, 230) and 4.47 log10c/mL (3.9, 4.9), respectively. Median number (range) of prior ART drugs was 18 (10, 23). Twenty one (78%) subjects achieved plasma HIV-1 RNA