Exploratory study comparing the metabolic toxicities of a lopinavir/ritonavir plus saquinavir dual protease inhibitor regimen versus a lopinavir/ritonavir plus zidovudine/lamivudine nucleoside regimen

OBJECTIVES: To assess the safety, efficacy and metabolic toxicity of lopinavir/ritonavir + saquinavir or zidovudine/lamivudine and evaluate the pharmacokinetics of lopinavir/ritonavir + saquinavir. METHODS: HIV-1-infected, antiretroviral-naive subjects were randomized to lopinavir/ritonavir (400/100 mg) twice daily + saquinavir (800 mg) or zidovudine/lamivudine (150/300 mg) in a Phase II, 48 week study. Subjects receiving lopinavir/ritonavir + zidovudine/lamivudine initiated escalating doses of saquinavir (400, 600 and 800 mg) weekly for 3 weeks. RESULTS: By intent-to-treat (non-completer = failure) analysis, 10/16 (63%) lopinavir/ritonavir + saquinavir-treated and 7/14 (50%) lopinavir/ritonavir + zidovudine/lamivudine-treated subjects achieved plasma HIV-1 RNA <50 copies/mL (P=0.713) at week 48. Safety, tolerability, metabolic changes and truncal fat increases were similar between groups. Small decreases in the lower extremity fat in the zidovudine/lamivudine group (-6%) and a statistically significant increase in the lower extremity fat in the saquinavir group (+19%) were observed. Lopinavir/ritonavir co-administered with saquinavir 600 or 800 mg twice daily produced saquinavir concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily. CONCLUSIONS: Treatment regimens had similar efficacy and tolerability. Metabolic parameters suggested lipoatrophy in the zidovudine/lamivudine treatment group. Saquinavir 600 and 800 mg twice daily produced concentrations similar to those previously reported for saquinavir/ritonavir 1000/100 mg twice daily.