A sensitivity analysis was performed after including only the first GRT pair

per patient. We also simulated a hypothetical situation in which all patients included in the study, at the end of a prolonged period of unsuppressed viraemia while receiving an NNRTI, would be switched to an etravirine-containing regimen which, as a result of the accumulation of NNRTI mutations over t0–t1, would have a certain predicted diminished activity at t1. The Rega IS was again used to derive the predicted susceptibility at both t0 and t1. The difference in etravirine predicted activity between t0 and t1 was calculated, averaged, standardized per time between t0 and t1, and used as a measure of the decrease in susceptibility to etravirine caused by the accumulation of NNRTI resistance. Ruxolitinib nmr A total of 227 patients were included in the study, who remained on a virologically failing NNRTI-based regimen and contributed 467 pairs of GRTs, with the following distribution: Talazoparib ic50 124 patients contributed one pair, 55 contributed two pairs, 25 contributed three pairs, nine contributed four pairs and 14 contributed more than four pairs. The breakdown of these contributions is given in Table 1a, which also shows the main characteristics of the target population. Only six of the

35 female patients included (17%) had a history of pregnancy prior to baseline-t0. Two hundred and eighty-eight patients with at least one GRT pair were excluded because there was no evidence that they experienced virological failure because of resistance (supporting information, Table S3). At t0, the median viral load of the patients was 4.18 log10 copies/mL [interquartile RAS p21 protein activator 1 range (IQR) 3.45–4.77 log 10 copies/mL] and the

median CD4 count was 222 cells/μL (IQR 130–367 cells/μL). In the 48 patients with a viral load measurement before the initiation of ART, the median viral load suppression below this value at t0 was 0.40 log10 copies/mL (range –2.26 to 3.30 log10 copies/mL; Table 1b), suggesting that HIV was somewhat suppressed compared with its maximum level of replication. Over the intervals t0–t1 (with a median of 6 months between tests and a median number of two viral load values over this time period), the viral load was observed to be stable mean change+0.17 [standard deviation (SD) 1.83] logs10 copies/mL per year; P=0.12 and a small increase in CD4 count was found [mean change+21 (SD 312) cells/μL per year; P=0.15]; the changes in these variables were not significantly different from zero. The corresponding figures for 178 patients who received an NNRTI-based regimen without a PI were +0.29 (SD 1.52) copies/mL per year (P=0.01) for viral load and +53 (SD 353) cells/μL per year (P=0.04) for CD4 cell count. There was no difference in the median time between GRTs between patients receiving nevirapine (median 6 months; IQR 3–9 months) and those receiving efavirenz (median 6 months; IQR 3–8.5 months; Wilcoxon test, P=0.73).