A once-daily lopinavir/ritonavir-based regimen provides noninferior antiviral activity compared with a twice-daily regimen

Objective: To evaluate the safety and noninferiority and to explore the efficacy of administration of once-daily versus twice-daily lopinavir/ritonavir (LPV/r) in antiretroviral-naive HIV-1-infected subjects. Design: Randomized, open-label, multicenter, comparative study. Methods: One hundred ninety anti retroviral-naive subjects with plasma HIV-1 RNA level > 1000 copies/mL and any CD4(+) cell count were randomized to lopinavir/ritonavir at a dose of 800/200 mg administered once daily (n = 115) or lopinavir/ritonavir at a dose of 400/100 mg administered twice daily (n = 75). Subjects also received tenofovir disoproxil fumarate (TDF) at a dose of 300 mg and emtricitabine (FTC) at a dose of 200 mg administered once daily. Results: The median baseline plasma HIV-1 RNA level and CD4(+) count were 4.8 log(10) copies/mL and 216 cells/mm(3), respectively. Before week 48, 20% (once daily) and 29% (twice daily) subjects discontinued. Virologic responses of the subjects through 48 weeks were comparable; 70% (once daily) and 64% (twice daily) achieved an HIV-1 RNA level < 50 copies/mL by intent-to-treat, noncompleter = failure analysis. No subject demonstrated LPV or TDF resistance, but 3 subjects (2 in the once-daily group, I in the twice-daily group) demonstrated FTC resistance. Mean increases in CD4(+) count were similar. Diarrhea (16% in the once-daily group, 5% in the twice-daily group; P = 0.036) was the most common moderate or severe study drug-related adverse event. Conclusions: Through 48 weeks, a once-daily regimen of lopinavir/ritoDavir + TDF + FTC appears to have similar virologic and immunologic responses in antiretroviral-naive subjects as the same regimen with lopinavir/ritonavir administered twice daily. Both regimens were relatively well tolerated, and no LPV or TDF resistance was observed.