Immune activation throughout a boosted darunavir monotherapy simplification strategy. (10th February 2014)

• Record Type: Journal Article
• Authors: BenMarzouk‐Hidalgo, O. J.; Torres‐Cornejo, A.; Gutiérrez‐Valencia, A.; Ruiz‐Valderas, R.; Viciana, P.; López‐Cortés, L. F.; Antonelli, G.
• Is Part Of: Clinical microbiology and infection. Volume 20:Number 12(2014:Dec.)
• Page Start: 1297
• Page End: 1303
• Publication Date: 2014-02-10
• Subjects: Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1111/1469-0691.12521
• Languages: English
• ISSNs: 1198-743X

Abstract

<abstract abstract-type="main" id="clm12521-abs-0001"> <title>Abstract</title> <p>Our aim was to assess the evolution and the impact that blips, intermittent low‐level viraemia and virological failure (VF) episodes have on patients' immune activation (IA) profiles during ritonavir‐boosted darunavir monotherapy (mtDRV/rtv). A prospective cohort of human immunodeficiency virus‐1‐infected patients who switched to mtDRV/rtv was followed for 2 years. Cellular IA was assessed according to HLA‐DR and CD38 expression in CD4<sup>+</sup> and CD8<sup>+</sup> T‐cells and their naïve, effector memory and central memory subpopulations, and systemic IA was evaluated according to sCD14 and D‐dimer levels. Seventy‐five patients from the MonDAR cohort were selected for this substudy, and classified according to viral outcome as having continuous undetectable viraemia (<italic>n</italic> = 19), blips (<italic>n</italic> = 19), intermittent viraemia (<italic>n</italic> = 21), and VF (<italic>n</italic> = 16). The IA profile was closely linked to viral behaviour. Patients on viral suppression for 24 months showed a significant decrease in CD4<sup>+</sup> and CD8<sup>+</sup> T‐cell activation and sCD14 and D‐dimer levels. Patients with transient low‐level viraemia episodes (blips and intermittent viraemia) showed cellular and systemic IA similar to baseline values. In contrast, significant increases in T‐cell activation and sCD14 and D‐dimer levels were observed in patients with VF. Baseline levels of HLA‐DR<sup>+</sup>CD38<sup>+</sup>CD8<sup>+</sup> T‐cells of >6.4% were independently associated with the emergence of VF. Therefore, mtDRV/rtv might be considered as a safe simplification strategy, on the basis of the IA results, whenever viral replication is under medium‐term and long‐term control. Transient low‐level viraemia episodes do not affect patients' IA status. Moreover, HLA‐DR<sup>+</sup>CD38<sup>+</sup>CD8<sup>+</sup> T‐cell baseline levels should be considered when patients are switched to mtDRV/rtv.</p> </abstract>