93 (95% CI 0.74–5.07). We then focused our attention on the risk of having a TBT WGS>2. As shown in Table 1, some differences were found in comparison to the analysis of at least three TMC125 RAMs. Of interest, a strong predictor of a decreased phenotypic susceptibility to TMC125 was a higher HIV RNA value (maximum risk at >5 log10 copies/mL),

with the AOR increasing from 2.62 for HIV RNA (<3.7 log10 copies/mL; 95% CI 1.35–5.10; P=0.004) to 3.99 for HIV RNA (>5 log10 copies/mL; 95% CI 1.98–8.04; P<0.001). NVP exposure retained an increased risk of a TBT WGS>2 (AOR 1.76; 95% CI 1.42–2.18; P<0.001), whereas previous EFV find protocol treatment did not. Duration of NNRTI therapy and previous exposure to one NNRTI did not have any significant effect, whereas exposure to two NNRTIs still had a significant effect, with an AOR of 2.26 (95% CI 1.05–4.88; P=0.038). The prevalence of TMC125-related mutations in the ARCA cohort was 68%. According to the DUET studies [7,8], Y181C, G190A, K101E and A98G were the mutations more frequently represented. The DUET studies showed that at least three TMC125-associated

mutations were required to impair the efficacy of the drug [7,8]. ABT-263 in vitro In our cohort, only 9.8% of sequences showed at least three TMC125-associated mutations, suggesting that the existence of this condition is infrequent even in patients with evidence of resistance to the other NNRTIs. V179F, Y181V and G190S, which have the most pronounced Palmatine effect on the response, were present in <5% of sequences. When at least three TMC125 RAMs were present, the mutations most frequently represented were confirmed to be Y181C, G190A and K101E,

but not A98G. In this setting, the prevalence of V179F, Y181C and G190S also increased. Y181C, a common mutation which confers resistance to other NNRTIs and to TMC125 when associated with two or more TMC125 RAMs and which was highly prevalent (32.2%) in the Tibotec data set [16], was associated with at least two mutations in a higher percentage of sequences in this study than found in the DUET studies (27%vs. 15%, respectively) [7], but it was present with V179F and G190S in <5% of sequences. The association of Y181C with G190A, K101E and A98G was statistically significant. The prevalence of V179F was low, but when associated with at least two mutations was present in 57% of sequences and was associated most frequently with Y181C, but was never associated with G190S or Y181V. Y181V and G190S, the other mutations with a large impact on response, were associated with at least two mutations in a low percentage of sequences.