However, where there is a risk of frequent prolonged treatment interruptions, EFV-based regimens may be associated with more frequent selection for drug resistance compared with PI/r. Clinicians are poor at both predicting future adherence to ART in naïve

subjects [11] and at detecting non-adherence during ART [12, 13]. However, in a case where a clinician or patient has concerns about a patient’s future adherence, should this influence the choice of first-line therapy? The consequences of low adherence depend on drug pharmacokinetics, potency, fitness of resistant strains and genetic barrier to resistance [14]. Hence, both the level and pattern of non-adherence must be considered. Large RCTs of first-line therapy may not be able to inform this choice as subjects likely to be non-adherent are often excluded from such trials. On the other hand, observational studies often select patients already established on ART [15, 16] ERK screening where the observed effects of non-adherence on treatment outcome are likely to differ from those in patients starting ART de novo. This selection bias may exclude those who have http://www.selleckchem.com/products/bay80-6946.html either experienced early virological failure, disease progression (or even death) or have defaulted from care. In addition, most studies either pre-date the use of boosted-PI regimens in first-line therapy [15, 17] or include large numbers of patients on unboosted

PI regimens. Three different outcomes may be considered: virological suppression, selection of drug resistance, and effect of pattern of non-adherence. There are no data from RCTs that directly address this question. Among subjects reporting <95% adherence in a RCT comparing LPV/r with once-daily DRV/r, virological failure was more likely in the LPV/r arm [18]. Among patients who were virologically suppressed initially, adherence <95% was associated with an increased risk of failure

[16], and very low adherence (<50%) results in virological rebound irrespective of regimen [5, 16, 19]. However, virological suppression has been observed with only moderate adherence (50–75%) heptaminol among patients on NNRTIs [5, 16, 19] and virological failure has been reported to be significantly more likely among all patients on unboosted PI-based regimens where adherence was <95% [16]. However, this finding may have been confounded by the once-daily dosing in the EFV group. A further study [20] examined only patients with undetectable viraemia and found no difference in rates of virological rebound for patients on PI/r vs. NNRTIs. The effect of level of non-adherence on selection of drug resistance varies by class. This was first described for unboosted PI regimens where moderate-to-high adherence was associated with increased risk of resistance [21]. The incidence of resistance in studies of boosted-PI regimens is low [18, 22-26] but is observed with adherence just below 80–95% [15, 27].