Objectives: To assess the safety, efficacy of atazanavir (400 and 600 mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir (400 mg/400 mg) twice daily with two nucleoside reverse transcriptase inhibitors (NRTIs) in highly active antiretroviral therapy failure.
Design and methods: Randomized, multinational, 48-week, pilot trial with antiretroviral-experienced patients having at least 1000 HIV-1 RNA copies/ml, 100 x 106 CD4 cells/l (75 x 106 cells/l without AIDS diagnosis) and virological response to a prior regimen. Efficacy was evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks.
Results: Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44, 1.19 and 1.66 log(10) copies/ml (P = NS) and comparable virological response (> 1.0 log(10) decrease HIV-1 RNA or HIV-1 RNA < 400 copies/ml) was achieved in 41, 29 and 35% (P = NS); and mean CD4 cell increases, 109, 55 and 149 x 106 cells/l in atazanavir 400-mg, atazanavir 600-mg and ritonavir groups, respectively. There were fewer adverse event discontinuations in the atazanavir groups (9%, 11%) versus the ritonavir group (30%) and atazanavir lacked adverse effects on lipids. In the atazanavir 400-mg, atazanavir 600-mg and ritonavir groups the mean changes from baseline at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol concentrations were -0.6, -6.7 and 23.2%, respectively and in fasting triglyceride concentrations they were -4.8, -27.1 and 93.0%, respectively (P < 0.05, LDL cholesterol; P < 0.001, fasting triglyceride; atazanavir/saquinavir versus ritonavir/saquinavir).
Conclusions: In antiretroviral-experienced patients, once-daily atazanavir/saquinavir was safe and well tolerated, showing comparable efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs. Small lipid changes from baseline with atazanavir/saquinavir were not clinically significant in comparison with the prompt, marked and sustained changes of a magnitude suggesting clinical relevance achieved in the ritonavir/saquinavir group.