Impact of prior PI usage on Week 48 responses to tipranavir boosted with ritonavir (TPV/r)

The Phase III RESIST trials demonstrated that TPV/r was significantly more effective than an optimized comparator PI/r (CPI/r). This analysis assessed the impact of previous PI use on various outcomes at Week 48. Methods RESIST patients had ≥3-class ARV experience, including ≥2 PI-based regimens; any CD4 cell count; viral load (VL) ≥1000 copies/mL; and HIV isolates carrying ≥1 primary PI mutation and ≤2 mutations at 33, 82, 84, 90. Patients were randomized to receive TPV/r (500 mg/200 mg BID) or pre-selected CPI/r plus optimized background regimen. Treatment response (TR) was defined as a confirmed ≥1 log10 copies/mL decrease in VL from baseline without treatment change. Results 1483 patients were randomized: 746 TPV/r; 737 CPI/r. Baseline mean CD4 cell counts: 196/195 cells/mm3; mean VLs: 4.73/4.73 log10 copies/mL in TPV/r and CPI/r arms respectively. Greater proportions of patients in the TPV/r arm had a TR or VL <400 or <50 copies/mL than control patients. With increased PI experience, responses to CPI/r were impaired to a greater extent than those to TPV/r. Week 48 virological responses TPV/r CPI/r Prior PIs* TR (%) % <400 % <50 TR (%) % <400 %<50 cp/mL cp/mL cp/mL cp/mL 2 42.5 41.3 35.0 34.3 32.9 24.3