rd triple therapy. Regarding the most suitable drugs to construct an effective dual regimen, data from salvage trials highlight the pivotal role of ritonavir boosted darunavir in rescue regimens. Because of its potency, high genetic barrier and resistance profile, darunavir was a main component of salvage Roscovitine Seliciclib therapy both in heavily pretreated patients and in those with less advanced disease.1,7 Furthermore, once daily darunavir dosing has proven to be as effective as twice daily dosing in selected patients with no darunavir associated mutations, which may facilitate the construction of a more convenient once daily regimen.20 Concerning selection of the second drug, etravirine in combination with darunavir has shown an impressive efficacy in pooled analysis from DUET studies.
25 Furthermore, etravirine is generally well tolerated with few side effects, and allows AZD1152-HQPA Aurora Kinase inhibitor the construction of a oncedaily regimen.26 However, it should be borne in mind that in patients previously failing a first generation NNRTI based regimen, minority resistant variants, which might have a negative impact on etravirine activity, are common and not detected by population sequencing.27 Tenofovir, when full activity is preserved, can be an attractive option considering its potency, simple dosage, long experience in use and moderate cost. In patients with CCR5 tropism, maraviroc may be useful to construct a potent and convenient once daily regimen in combination with darunavir.21 Raltegravir, in spite of its high price and twice daily dosing, is a potent and very well tolerated antiretroviral drug that may be very useful to construct an effective dual regimen in combination with PI/r.
28 In our study, dual therapy was well tolerated and improved treatment convenience, compared with the failing regimen XAV-939 in 40% of patients. In contrast, construction of a triple standard therapy in this population would have to use more complex regimens, 29,30 which might have a negative impact on adherence and treatment outcome. In fact, therapeutic failure was mainly due to intolerance or lack of adherence, and a true OT viral failure due to insufficient antiviral potency was observed in just one patient. These data highlight the importance of efforts to improve treatment adherence and reinforce the idea of an individually based approach taking into account not only cumulative resistance mutations and historical treatment but also the patient,s needs and tolerances to previous regimens as the best strategy to optimize treatment outcome in pre treated patients on failing antiretroviral therapy.
The present study has some potential limitations. The first is the lack of a control group to compare with this new strategy, however, the rate of viral response was very high and similar to that observed with standard triple therapy.7,31 Secondly, the heterogeneity of the rescue regimens might hinder the interpretation and extrapolation of the results. Nevertheless, almost 80% of patients received darunavir as a pivotal drug, in combination with etravirine, tenofovir or raltegravir. Consequently, although a two component fully active regimen based on ritonavirboosted atazanavir32 or lopinavir33,34 can achieve and maintain viral suppression in patients with no PI related mutations, the results of our study