PLX-4720 Of all patients, 90% had,50 copies/mL at week 48 of treatment and almost 85% remained free of therapeutic failure after a median follow up of 16 months. Furthermore, a significant increase in CD4 T cell count was observed during the first 48 weeks of treatment, similar to that observed in other studies.19,20 Although cross study comparisons must be undertaken with caution, the efficacy results seen in our study are consistent with previously reported data from trials conducted in similar settings.7,20 In the TMC114 C214 study,7 the efficacy and safety of ritonavir boosted darunavir and ritonavir boosted lopinavir, both in combination with an OBR, were compared in 595 pre treated patients on viral failure. At treatment week 48, 71% of subjects in the darunavir arm and 60% in the lopinavir arm achieved virological suppression to,50 copies/mL.
Overall, 33% of these patients had, at most, one active drug in the OBR. In a stratified analysis of patients treated with darunavir, 80% with one active drug in the OBR, and 68% with at least two active drugs, had,50 copies/ mL at week 48. Corresponding data in Cyclopamine Hedgehog inhibitor the lopinavir arm were 57% and 61%.7 The high efficacy of darunavir plus one additional fully active drug was also observed in the context of heavily pre treated patients. In a pooled subgroup analysis of data from the POWER trials, no differences were seen in the percentage of patients with less than 50 copies/mL at week 48 of treatment, with ritonavir boosted darunavir among patients with one active drug in the OBR compared with those with at least two active drugs in the OBR.
1 Even though it is not powered to show significant effects within a subgroup, stratified analysis of salvage trials provides relevant information regarding which factors are associated with viral response, and could contribute to explaining the results of this study. In the POWER trials, 80% of patients with viral load,20000 copies/mL achieved viral suppression, TGX-221 compared with 29% of those with.20000 copies/mL at baseline.1 A lower pre treatment viral load was also independently associated with higher rates of viral response to salvage regimens containing new drugs in other clinical trials.21 23 In our study, median viral load at baseline was low and was probably an important determinant of the high viral response.
Another factor associated with the likelihood of achieving viral suppression with a darunavir containing salvage regimen is the number of RAMs in the protease gene, and in particular the number of specific darunavir associated mutations. A loss of response to darunavir occurs with the first mutation, increasing linearly with additional mutations, and beyond three mutations the response is greatly reduced.1,24,25 The low number of PI related mutations and in particular the low percentage of patients with darunavir associated mutations may contribute to explaining the high efficacyobserved in our study. Other factors, such as the preserved immune status of patients evaluated in the present study, could also contribute to explaining the excellent treatment outcome.7,21 23 These data taken together suggest that in selected patients with predictors of viral response a PI/r based rescue regimen employing only two active drugs might be as effective as standa