In HIV-infected patients with no darunavir resistance–associated mutations, once-daily darunavir is as effective as twice-daily darunavir, with fewer adverse events.

Darunavir was initially approved for treatment-experienced patients at a dose of 600 mg, with 100 mg of ritonavir, twice daily. However, data from the POWER 1 and 2 trials suggested that the once-daily dose approved for use in treatment-naive patients — 800 mg, with 100 mg of ritonavir — might also be effective in treatment-experienced patients with no baseline darunavir resistance. The ODIN trial, a phase III, open-label, manufacturer-funded study, was designed to evaluate this possibility.

A total of 590 patients who were on a failing regimen and had no darunavir resistance–associated mutations were randomized to receive ritonavir-boosted darunavir either once daily (800 mg, with 100 mg of ritonavir) or twice daily (600 mg, with 100 mg of ritonavir). Both groups received optimized background regimens consisting of 2 nucleoside reverse transcriptase inhibitors. Forty-six percent of the patients had never received a protease inhibitor (PI) before, and 84% of the patients had no major PI mutations.

At week 48, 72% of the once-daily group and 71% of the twice-daily group achieved viral loads <50 copies/mL, establishing noninferiority of the once-daily dose. Only one patient with virologic failure (in the once-daily group) developed major PI mutations. The once-daily group had fewer triglyceride elevations and lower cholesterol levels (total and LDL) than the twice-daily group.

Comment: Based on the results of this trial, on December 13, 2010, the FDA approved once-daily dosing of ritonavir-boosted darunavir for treatment-experienced patients with no darunavir resistance–associated mutations. As the authors point out, most treatment-experienced patients do not have such mutations. For the subset of patients who do, twice-daily dosing should continue to be used.

Published in Journal Watch HIV/AIDS Clinical Care