Comment on: Aminoglycoside drugs in clinical practice: an evidence-based approach

Dr Parienti reminds us, in his comments on the DAUFIN trial, that simpler is not always better, even if the adherence rate was better with once-daily regimens than with twice-daily regimens according to a recent meta-analysis (but the effect was only modest and more pronounced at the time of treatment initiation). Treatment interruptions are a risk factor for non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance development, but no difference has been shown when nevirapine was administered once or twice a day. More early virological failures with resistance to efavirenz have been observed with didanosine/lamivudine/efavirenz once a day compared with zidovudine/lamivudineþ efavirenz twice a day, but the adherence rate was not different between treatment arms; therefore, the resistance mutations are probably more associated with the NRTI background choice. Despite a non-optimal adherence rate with the once-daily regimen in the DAUFIN trial, the high virological failure rate remains unexplained, and the same virological failures have been observed in a study by Lapadula et al., which evaluated the tenofovir, emtricitabine and nevirapine combination, but with a twice-a-day nevirapine administration. Finally, if we agree that simpler is not always better, on the other hand, it is not worse. According to clinical trials, as well as real life, most of the patients on antiretroviral treatment remain in virological success while more and more combinations are administered once daily.