RESIST-1: A phase 3, randomized, controlled, open-label, multicenter trial comparing tipranavir/ritonavir (TPV/r) to an optimized comparator protease inhibitor/r (CPI/r) regimen in antiretroviral (ARV) experienced patients: 24-week data.  

 

Charles Hicks and the RESIST-1 study team. Duke University Medical Center, Durham, NC.

Background: TPV is a non-peptidic PI with potent activity in ARV-experienced HIV+ persons. This randomized, controlled, open-label phase 3 trial compared efficacy and tolerability of TPV/r to CPI/r in ARV-experienced patients.

Methods: Patients with ≥3-class ARV experience including ≥2 PI-based ARV regimens and ≥1 primary PI mutation (but ≤2 at amino acids 30, 82, 84, 90), and viral load (VL) >1000 copies/mL were eligible. Before randomization, an optimized CPI/r regimen [which could include enfuvirtide (ENF)] was selected. Patients were then randomized to TPV/r (500 mg/200 mg) or CPI/r. For this planned 24-week analysis, treatment response was defined as a confirmed ≥1 log₁₀ decrease in VL from baseline (BL).

Results: 620 patients were randomized at 125 sites in North America and Australia: 311 to TPV/r and 309 to CPI/r. Selected CPI was LPV (61%), SQV (21%), APV (14%), or IDV (4%). BL characteristics were similar for the 2 arms: median VL was 4.81 (TPV/r) and 4.84 (CPI/r) log₁₀ copies/mL, and BL CD4 was 123 cells/mm³ in both arms. Patients had previously received a median 6 NRTIs, 2 NNRTIs, 4 PIs; 12.3% had taken ENF. By ITT-NCF at week 24, treatment response was seen in 41.5% in the TPV/r arm vs 22.3% in the CPI/r arm (weighted difference 18.4%; 95% CI for difference 11.4 to 25.3%, P< 0.0001). TPV/r was superior to CPI/r in proportion of patients with VL <400 copies/mL (34.7% TPV/r vs 16.5% CPI/r) and <50 copies/mL (25.1% vs 10.0%), P<0.001. Median CD4 change was +36 cells/mm³ in the TPV arm vs +6 cells/mm³ in the CPI arm (ITT-LOCF), P<0.001. Adverse event profiles were similar although the TPV/r arm had a higher rate of ALT and lipid elevations; most were transient and asymptomatic. Only 2  patients discontinued TPV/r for >grade 3 ALT/AST elevations.

Conclusion: In ≥3-class ARV treatment-experienced patients, TPV/r was superior to currently available CPI/r in suppressing HIV at 24 weeks.