The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1250mg twice-daily regimen in HIV-infected patients

Objectives To evaluate the long-term pharmacokinetics and safety of adding ritonavir 100 mg twice-daily to a nelfinavir 1250 mg twice-daily regimen in HIV-infected patients. Methods This was a prospective, randomized, open-label, controlled 24-week study. Sixteen patients receiving a nelfinavir 12 50 mg twice-daily regimen with plasma viral load < 1000 HIV-1 RNA copies/mL were randomized to continue treatment or to have ritonavir 100 mg twice-daily added. Safety, including fasting lipid levels, was evaluated at weeks 4, 12 and 24. Patients who were randomized to have ritonavir added (n = 9) participated in three 12-h pharmacokinetic evaluations at baseline, week 4 and week 24. Results Increases in median nelfinavir steady-state plasma concentrations at 12 h (Cl 2) from 512 to 773 ng/ mL [median difference 450 ng/mL; 9 5% confidence interval (CI) 116-15 10 ng/mL] and in median active nelfinavir metabolite M8 C-12 from 107 to 603 ng/mL (median difference 545 ng/mL; 9 5% CI 370-891) were seen after the addition of low-dose ritonavir (baseline to week 24). There were no differences between the nelfinavir or M8 pharmacokinetic parameters at weeks 4 and 24. No significant changes or differences in the concentration of fasting total cholesterol, low-density lipoprotein (LDL) cholesterol or total triglycerides or in the occurrence of adverse events were observed within or between the two groups. Conclusions Nelfinavir and especially M8 concentrations are increased when low-dose ritonavir is added to a nelfinavir-containing regimen. The combination seems to be safe and the nelfinavir/ritonavir regimen could be an option in patients with low nelfinavir + M8 concentrations.