title: Immune activation throughout a boosted darunavir monotherapy simplification strategy.
abstract: 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(+) and CD8(+) 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 (n = 19), blips (n = 19), intermittent viraemia (n = 21), and VF (n = 16). The IA profile was closely linked to viral behaviour. Patients on viral suppression for 24 months showed a significant decrease in CD4(+) and CD8(+) 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(+)CD38(+)CD8(+) 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(+)CD38(+)CD8(+) T-cell baseline levels should be considered when patients are switched to mtDRV/rtv.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: O J
authors.initials: OJ
authors.lastname: BenMarzouk-Hidalgo
authors.forename: A
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez-Valencia
authors.forename: R
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: P
authors.initials: P
authors.lastname: Viciana
authors.forename: L F
authors.initials: LF
authors.lastname: López-Cortés
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000069454:Darunavir; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D005338:Fibrin Fibrinogen Degradation Products; D013449:Sulfonamides; C036309:fibrin fragment D; D019438:Ritonavir; D000069454:Darunavir
keywords: Boosted protease inhibitor monotherapy; HIV infection; immune activation