In this study, Abbott compared once-daily with twice-daily lopinavir/ritonavir (LPV/r, Kaletra) (both in combination with tenofovir [TDF, Viread] and emtricitabine [FTC, Emtriva]) in antiretroviral-therapy-naive patients. The results of the study have been presented previously, showing that once-daily lopinavir/ritonavir was not inferior to the twice-daily formulation based on virologic outcome. The purpose of the analysis presented here was to investigate whether responses to once or twice-daily treatment depended on the patient's stage of HIV disease (based on CD4+ cell count and viral load) or trough lopinavir concentrations.

One hundred and ninety patients were randomized in a 3:2 ratio to once or twice-daily therapy. Pre-dose (trough) concentrations of lopinavir were obtained at weeks 4, 8, 16, 24 and 48.

At baseline, approximately 45% of the patients had a CD4+ cell count less than 200, and 38% of the patients had baseline HIV RNA above 100,000 copies/mL. As noted previously, 70% of the once-daily group and 64% of the twice-daily group achieved a viral load of less than 50 at week 48 by intention-to-treat analysis, meeting non-inferiority criteria. Comparing responders with nonresponders, the study found no association between lopinavir trough concentrations, baseline HIV RNA or baseline CD4+ cell count.

These data are reassuring with regard to once-daily lopinavir/ritonavir therapy, as they confirm that even though trough concentrations may be lower than when the drug is given twice daily, the drug levels are more than sufficient when treating protease inhibitor susceptible virus.

A sigmoidal concentration-response curve is suggested, where the majority of patients treated with either once or twice-daily lopinavir/ritonavir are at the flat end of the drug concentration curve.

In addition, the study affirms the good response to lopinavir/ritonavir regimens, even in patients with advanced HIV disease. As gastrointestinal symptoms were more frequent in the once-daily treatment arm, widespread use of this agent in such a fashion likely awaits an improved and better tolerated formulation, work on which is ongoing.