A Randomized Trial of Nelfinavir, Ritonavir, or Delavirdine in Combination with Saquinavir-SGC and Stavudine in Treatment-Experienced HIV-1-Infected Patients

PURPOSE: To evaluate the 24-week impact of saquinavir-enhancing antiretroviral therapy on viral replication in patients previously treated with nucleoside analogues with or without prior saquinavir hard-gel capsules (HGC). METHOD: Patients were randomized in three groups to receive the following: Group 1-nelfinavir (750 mg tid), saquinavir soft-gel capsule (SGC) (800 mg tid), and stavudine (40 mg bid); Group II-ritonavir (400 mg bid), saquinavir-SGC (400 mg bid), and stavudine (40 mg bid); or Group III-delavirdine (400 mg tid), saquinavir-SGC (800 mg tid), and stavudine (40 mg bid). Viral loads, CD4 count, and safety were assessed over a 24-week period with an additional 6-month follow-up. RESULTS: 73 patients received randomized therapy; 14 of whom were SQV naïve, with a median baseline viral load of 3.6 log(10) and a CD4 count of 370 cells/mm(3). By 6 months, the median decreases in plasma viral loads were 0.26, 0.71, and 0.29 log(10) copies/mL for groups I, II, and III, respectively. The median increases in CD4 counts, for groups I, II, and III, were 52, 40, and 69 cells/mm(3) at 6 months, respectively. Changes in viral load and CD4 counts at 6 months and 1 year were not significantly different between the treatment groups. More patients discontinued therapy in the ritonavir arm (35%) for drug intolerance or toxicity compared to either the nelfinavir or delavirdine arms (15% and 5%, respectively). In a multivariate analysis, baseline viral load, younger age, and baseline saquinavir resistance were significantly associated with detectable viral load at 24 weeks. CONCLUSION: The use of antiretroviral agents that pharmacokinetically boost saquinavir levels has a modest benefit in saquinavir-experienced patients.