A randomized clinical trial comparing nelfinavir and ritonavir in patients with advanced HIV disease (CPCRA 042/CTN 102)

Purpose: To compare the long-term clinical efficacy and toxicity of initial strategies of nelfinavir (NFV) or ritonavir (RTV) in patients with CD4+ cells below 200/mm³. Method: This was an open-label randomized multicenter trial (CPCRA, CTN). Patients were naïve to protease inhibitor use except for hard gel saquinavir. Patients who were intolerant to their assigned therapy were allowed to switch arms (later RTV-intolerant patients could switch to indinavir). The primary objective was to compare the regimens for AIDS-defining conditions and death (AIDS/death) using intent-to-treat analysis. Hazard ratios (HR) for NFV and RTV were estimated using Cox's proportional hazards models. Kaplan-Meier life table summaries were also used to compare the two groups. Results: There were 775 patients who were randomized beginning in January 1997 and followed through December 2001. At entry, mean CD4+ cell count was 58 cells/mm³ and HIV RNA level averaged 4.9 log copies/mL. After a median follow-up of 52 months, rates of AIDS/death were 12.7 and 11.0 per 100 person years for the NFV and RTV groups, respectively (HR = 1.16; 95% CI, 0.92-1.46; p = .21). Discontinuations occurred earlier in the RTV group (p = .0001). Conclusion: There are moderate differences in efficacy and large differences in tolerability between a strategy of initial NFV or RTV in patients with advanced disease. Finding the right balance between potency and tolerability remains a challenge.