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] RG7422 chemical structure 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 Atezolizumab manufacturer 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%) Carbohydrate 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].