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We read with interest the recent article by Soriano et al. [1] on the ARTEN trial, comparing nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients. In this large randomized trial, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations occurred in 29/372 (7.8%) patients on nevirapine, while no protease inhibitor (PI) mutations were observed in the atazanavir arm. The nucleoside reverse transcriptase inhibitor (NRTI) mutations M184V and K65R occurred in 25 (6.7%) and 12 (3.2%) patients on nevirapine, respectively. Again, no NRTI resistance mutation was detected in the atazanavir arm. It is obvious that the problem of a higher failure rate due to resistance in comparison with a ritonavir-boosted PI (PI/r) is not unique to nevirapine. A similar pattern has been observed with efavirenz, when compared with lopinavir/r, both combined with two NRTIs [2]. A systematic evaluation of 20 studies with 7,949 patients showed that resistance mutations were significantly more common among NNRTI-treated patients, applying not only to NNRTI/PI resistance mutations but also to NRTI key mutations like M184V and K65R [3]. We think that the risk of 7.8% of NNRTI resistanceassociated virological failure and the even higher risk of any resistance in the ARTEN trial require a more detailed analysis. In order to better understand the extent and breadth of resistance development, it would be important to know the total number of patients in whom any mutation was selected, the time points at which resistance mutations were detected, and the number of patients in whom two-class resistance developed. Moreover, an analysis of predictive factors such as baseline plasma viraemia, CD4+ T-cells, ethnic groups or other factors would be necessary to define groups at high risk of failure with resistance. Some smaller trials evaluating tenofovir, emtricitabine and nevirapine observed an increased risk of treatment failure and the development of resistance, especially when baseline viral load was high [4,5]. As part of the attempt to maintain viral suppression for the entire life span of HIV-infected patients, physicians should be alerted to the possibility and the long-term consequences of failure with resistance. Every effort should be made to avoid selection of resistance. This principle should be applied not only to all NNRTIs but also to new drug classes such as integrase or entry inhibitors.