Variable adherence to prescribed dosing regimens for protease inhibitors: scope and outcomes.
OBJECTIVE
It is generally accepted that a high degree of adherence to the dosing regimens of protease inhibitors is essential to avoid virological failure. It is also believed that once-daily dosing of protease inhibitors, by improving adherence, will lead to better outcomes. This review will discuss the patterns of adherence for once-daily and twice-daily regimens and illustrate how differences in these patterns might favor twice-daily regimens in some settings.


RESULTS
Using electronic monitoring of more than 1800 patients enrolled in HIV clinical trials, the fraction of doses taken by patients on a once-daily regimen was about 10% higher than that taken by patients on a twice-daily regimen. However, patients on the twice-daily regimen were less likely to have their trough concentrations fall below a minimum effective concentration. In an outcome study that compared once-daily with twice-daily lopinavir/ritonavir, there was no difference in virological failure through 48 weeks, but patients with a viral load of more than 100 000 copies/ml had a greater probability of a sustained viral response on a twice-daily regimen.


CONCLUSIONS
Although patients and providers strongly favor once-daily regimens, recent clinical and model-based studies suggest that twice-daily protease inhibitor containing regimens may yield better outcomes in some settings. Continued reinforcement of adherence is necessary to improve both the execution of the drug regimen as well as continuation (persistence) with antiretroviral therapy.
Blaschke
Terrence F
TF
Division of Clinical Pharmacology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5130, USA.