574    

Background:  Indinavir plus ritonavir (IDV/r) has been compared in a randomized clinical trial to twice-daily saquinavir SGC plus ritonavir (SQV/r), but not to once-daily SQV/r. Simplified Protease Inhibitor Trial (SPRINT) was a prospective, randomized, open-label trial comparing once-daily SQV/r with twice-daily IDV/r, each with 2 reverse transcriptase inhibitors, with respect to proportions of patients with plasma viral load <50 copies/mL at 24 and 48 weeks.

Methods:  We randomized 164 HIV⁺ adults to receive either SQV/r 1600 mg/100 mg once daily or IDV/r 800 mg/100 mg twice daily, with either 2 nucleoside reverse transcriptase inhibitors (NRTI) or 1 NRTI plus 1 non-NRTI (NNRTI) as selected by the treating physician. Eligible patients had a viral load of > 5000 copies/mL and were either protease inhibitor- (PI-) naïve, or had no evidence of PI resistance. Viral load, CD4, safety labs, and fasting lipids and glucose were assessed at weeks 0, 4, 8, 12, 16, 24, 36, and 48. Follow-up was completed in March 2004. Categorical variables were compared between groups using the χ² Test or Fisher’s Exact Test, as appropriate. Continuous variables were compared using the Wilcoxon Rank Sum Test. Proportions were analyzed using the binomial test for 2 proportions. Viral load of > 100,000 (5.0 log₁₀) copies/mL were set to 5.0 log₁₀.

Results:  The efficacy analysis included 147 evaluable patients. At baseline, the SQV/r (n = 70) and IDV/r (n = 77) groups were similar with respect to:  median age of 40 years, 79% male, 80% PI-naïve, 62% viral load of >5.0 log₁₀ copies/mL, median CD4 130 cells/mm³. Background regimens included a NNRTI in 3 patients on IDV/r and 0 on SQV/r. The SQV/r and IDV/r arms did not differ with respect to proportions of patients with viral load of <50 copies/mL by intent-to-treat analysis at either week 24 (56%, 49%, p = 0.44) or week 48 (50%, 45%, p = 0.70). CD4 increases to week 48 were also similar between arms (SQV/r 147 cells/mm³, IDV/r 131 cells/mm³, p = 0.60). However, 29 of 77 (38%) patients discontinued IDV/r by week 48 due to adverse events, mainly renal or gastrointestinal, as compared with 10 of 70 (14%) who discontinued SQV/r (p < 0.01; 95% CI from IDV/r > by 8% to IDV/r > by 38%). No differences were observed between arms with respect to changes in fasting lipids or glucose from baseline to either week 24 or 48 (n = 89, p > 0.1).

Conclusions:  In patients with PI-susceptible HIV, once-daily SQV/r and twice-daily IDV/r, each with 2 reverse transcriptase inhibitors, are equally effective in achieving viral load of < 50 copies/mL at 24 and 48 weeks, and have similar effects on fasting lipids and glucose. However, the IDV/r arm had a higher rate of discontinuation due to adverse effects.

Keywords: protease inhibitors; saquinavir; indinavir