Ontology highlight
ABSTRACT: Objectives
Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.Methods
Thirty-four participants with virologic suppression ? 48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56+CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279).Results
Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) >50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL >50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels.Conclusions
Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring.Trial registration
ClinicalTrials.gov NCT00084019.
SUBMITTER: McKinnon JE
PROVIDER: S-EPMC4011688 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
McKinnon John E JE Mailliard Robbie B RB Swindells Susan S Wilkin Timothy J TJ Borowski Luann L Roper Jillian M JM Bastow Barbara B Kearney Mary M Wiegand Ann A Mellors John W JW Rinaldo Charles R CR
PloS one 20140506 5
<h4>Objectives</h4>Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification.<h4>Methods</h4>Thirty-four participants with virologic suppression ≥ 48 weeks on antiretroviral therapy (2 NR ...[more]