Only six patients underwent a switch in NNRTI between t0 and t1: four patients switched from nevirapine to efavirenz and two patients did the opposite and were classified according to their NNRTI exposure at t0. At the first GRT in a pair, the median number of drugs in the

regimen was 4 (IQR 3–4) and the most frequently used NRTIs at t0 together with the NNRTI were lamivudine (56%), stavudine (49%) and didanosine (36%). At t0, two NRTIs plus either nevirapine or efavirenz were used in 189 (41%) of the pairs while the remaining pairs were on combinations including PIs (Table 1b). The frequency of use of other antiretrovirals besides nevirapine/efavirenz at t1 was similar to that observed at t0 (data

not shown), suggesting Forskolin that these patients had in most cases been kept on the same drugs over t0–t1 despite virological failure. The median number of NNRTI mutations detected at baseline-t0 was 2 (range 0–8) and the majority of patients (66%) had at least one NNRTI mutation (supporting information, Table S4). For only 36 of the GRT pairs (8%) were no NNRTI mutations detected at both GRTs. In 2% of http://www.selleckchem.com/products/pci-32765.html the patients included in the study, NNRTI mutations were detected at the GRT performed prior to the estimated date of virological failure. Table 2a shows the prevalence of patients with at least one IAS NNRTI mutation, the distribution of individual IAS NNRTI mutations detected in major virus populations at t0 and the estimated proportions at t1. Table 2a also shows the total number of NNRTI mutations (overall and stratified by specific NNRTI drug) at t0 and t1, and the estimate of the rate of accumulation of NNRTI resistance over the observation period. The highest rate of accumulation was observed for mutations

103N (27.6 new mutations per 100 years; 95% CI 20.7–35.3), 181C (12.2/100 years; 95% CI 8.0–17.7) 190A (9.4/100 years; 95% CI 5.8–14.3) and Selleck Erastin 108I (6.7/100 years; 95% CI 4.0–10.6). Other mutations such as 98G, 100I, 101E, 181I and 188L were also accumulated, although at the lower rate of 0.2–0.4/100 years. The number of pairs for which there was at least one NNRTI mutation that was detected at t1 but not at t0 was 39/49 PYFU, giving a rate of accumulation of at least 0.79 new NNRTI mutations/year (95% CI 0.66–0.90; Table 2a). Overall, 180 IAS NNRTI resistance mutations were accumulated over 295 PYFU (average rate of 0.61 per year; 95% CI 0.55–0.67), while the rate of accumulation of NNRTI drug-specific mutations was somewhat slower, at 0.46/year, and that of etravirine mutations was a little lower compared with nevirapine or efavirenz mutations.