Predictive value of HIV‐1 replication capacity and phenotypic susceptibility scores in antiretroviral treatment‐experienced patients

Abstract

ObjectivesThe aim of the study was to determine the prognostic value of HIV replication capacity (RC) for subsequent antiretroviral (ARV) treatment response in ARV-experienced patients. MethodsRC and phenotypic resistance testing were performed at baseline and week 12 on plasma samples from patients randomized to undergo a 12-week ARV drug-free period (ARDFP) or initiate immediate salvage therapy (no-ARDFP group) in the Options in Management with Antiretrovirals (OPTIMA) trial. Dichotomous and incremental phenotypic susceptibility scores (dPSSs and iPSSs, respectively) were calculated. The predictive value of RC and PSS for ARV therapy response and/or ARDFP was evaluated using multivariate regression analysis and Pearson correlations. ResultsIn 146 no-ARDFP subjects, baseline RC (50.8%) did not change at week 12 and was not correlated with CD4 cell count or viral load changes at week 12 (P = 0.33 and P = 0.79, respectively) or at week 24 (P = 0.96 and P = 0.14, respectively). dPSS predicted virological but not CD4 cell count response to ARV therapy at weeks 12, 24 and 48 (P = 0.002, P < 0.001 and P = 0.005, respectively). RC was significantly correlated with dPSS and iPSS at baseline, but did not increase their predictive value. In the 137 ARDFP patients, RC increased significantly (from 52.4 to 85.8%), but did not predict CD4 cell count and viral load changes during ARDFP (P = 0.92 and P = 0.26, respectively). RC after ARDFP did not predict subsequent CD4 cell count and viral load changes 12 weeks following ARV treatment reinitiation (P = 0.90 and P = 0.29, respectively). ConclusionsWe found no additional predictive value of replication capacity for virological or immunological responses (above what PSS provides) in patients undergoing salvage ARV treatment.Keywords: antiretroviral therapy, HIV, phenotypic susceptibility score, replication capacity, resistance Accepted 27 October 2011 IntroductionIn clinical trials of effective HIV combination antiretroviral (ARV) regimens, the majority of study participants maintained virological suppression for 3-7 years [1][2][3]. However, the proportion of patients experiencing treatment failure in real-life clinical settings is reported to be somewhat higher [4][5][6], and these patients have an increased risk of HIV disease progression. Incomplete virological suppression is expected to lead to the emergence and accumulation of drug-resistant strains, which might jeopardize the success of future treatment options [7][8][9][10][11]. It is therefore important to improve our understanding of the In addition to genotypic and phenotypic testing, replication capacity (RC) is regularly used by clinicians when deciding on the strategy for the management of these treatment-experienced patients. A number of trials have determined that temporary interruption of ARV treatment is a strategy that leads to rapidly increased plasma HIV RNA, decreased CD4 T-cell count and increased risk for clinical progression [12][13][14]. However, interruption of a failing regimen results in a rapid inc...