This

suggests that HIV-1 may be constrained in its ability to become both highly resistant and highly fit, and that reduced viral fitness is an important factor contributing to persistent partial suppression of viral replication during long-term virological failure. Our results, exploring the predictive value of RC in the largest published cohort of treatment-experienced patients undergoing treatment YAP-TEAD Inhibitor 1 interruption, did not support these hypotheses. As reviewed by Martinez-Picado and Martinez [30], the association of RC and plasma HIV-1 RNA levels in patients with viraemia has been found to be either weak [31] or limited to small pilot cohorts [18]. There are limited published data on the predictive value of RC in treatment-experienced

patients in the HAART era [22]. Our results for the predictive value of PSS are in accordance with those of Lawrence et al. [32] and Katzenstein et al. [33] in demonstrating that PSS predicts early virological response to salvage HAART. Potential limitations of our study include the large diversity in treatment regimens that patients in our cohort received, AZD0530 ic50 given the fact that OPTIMA was a strategy trial rather than a specific combination regimen trial. We also did not account for the possibility of secondary failures resulting in alterations in the salvage regimens, but these are less likely to occur within the first 12 weeks. We limited our analysis to this early phase for this reason, and also because of the attrition in the number of

patients with samples available at the later time-points, which would limit our ability to assess the predictive value of both PSS and RC values at baseline. In summary, in this large cohort of ARV treatment-experienced patients undergoing different salvage treatment strategies, our results confirm that RC increases PLEK2 after treatment interruption and baseline PSS predicts changes in viraemia both during treatment interruption and early in salvage therapy. iPSS did not have a better predictive value than dPSS. The latter, easier measurement should be evaluated in predicting responses to the newer classes of ARVs. We further demonstrated that baseline RC does not predict changes in CD4 cell count during either treatment interruption or salvage therapy and does not provided added information to PSS. We thank all the subjects, investigators and staff who participated in the OPTIMA trial. This study was funded by the Department of Veterans Affairs Cooperative Studies Program and, in part, by a Department of Veterans Affairs grant to MH, and by Monogram BioSciences Inc., who provided support for performance of the PhenoSense™ and replication capacity assays.