Once‐Daily Regimen May Increase Drug Holidays

To the Editor—Molina et al. [1] showed good efficacy and safety of once-daily antiretroviral combination (ARV) therapy during the 24 first weeks of treatment with emtricitabine, didanoside, and efavirenz among 40 patients who were naive to treatment. Ease of administration of once-daily dosing represents a considerable advance in the quality of life of human immunodeficiency virus (HIV)–infected patients. Molina et al. investigated oncedaily highly active antiretroviral therapy regimens as a means of optimizing treatment adherence. However, the impact of oncedaily treatment on adherence is not clear from the medical literature. In a review of 57 publications on the relationship between patient adherence rate and medication dosing across a wide range of chronic illnesses [2], onceand twice-daily regimens were better than 3or 4-times daily regimens, but onceand twice-daily schedules were similar if we consider treatment adherence as the percentage of drugs taken. Recently, no difference in adherence was observed between nelfinavir given twice a day and efavirenz given once a day [3], although both were given with twice-daily dual nucleoside analogues. On the other hand, a twice-daily regimen is considered to be more reliable than a once-daily regimen if the first dose is missed [4]. In a study that compared onceand twice-daily dosages in clinical practice, Kruse et al. [5] reported that hypertensive patients went without medication for 48 h 3 times more frequently with a once-daily regimen than with a twice-daily regime ( ). P ! .05 Similarly, Paes et al. [6] showed a significantly higher number of 24-h periods without a dose with oncethan with twice-daily regimens among patients who were following an oral antidiabetic regimen. Because of an increase number of treatment interruptions among nonadherent patients [7], subtherapeutic ARV drug concentrations followed by HIV RNA rebound may lead to more-rapid K103N mutation, conferring cross-resistance [8] among efavirenz, nevirapine, and delavirdine and compromising a patient’s future treatment options for life. Further studies involving long-term assessment of adherence and follow-up for ARV resistance are needed to assess the clinical impact of once-daily versus twice-daily ARV regimens.