title: Assessment of chloroquine as a modulator of immune activation to improve CD4 recovery in immune nonresponding HIV-infected patients receiving antiretroviral therapy.
abstract: OBJECTIVE
  Chloroquine (CQ), an anti-inflammatory drug, inhibits Toll-like receptor (TLR) signalling in plasmacytoid dendritic cells (pDCs) and may be beneficial for HIV-infected patients in whom immune activation persists despite effective antiretroviral therapy (ART). The effect of CQ on CD4 T-cell recovery and immune activation in immune nonresponding patients receiving successful ART was therefore studied.
  
  
  METHODS
  Nineteen adults on ART with CD4 counts ≤ 350 cells/μL and undetectable viral load (VL) orally received CQ at 250 mg/day for 24 weeks. Side effects, CD4 and CD8 T-cell counts, VL, T-cell activation, pDC proportion and plasma inflammatory markers were assessed at baseline, at 24 weeks, and at 12 weeks after CQ discontinuation (clinicaltrial.org registration #NCT02004314).
  
  
  RESULTS
  CQ was well tolerated and all patients maintained an undetectable VL. The absolute CD4 and CD8 T-cell counts and their percentages, the pDC proportion, T-cell activation, D-dimer and C-reactive protein (CRP) plasma levels and the kynurenine/tryptophan ratio did not change with CQ treatment. Among nine cytokines/chemokines measured, only levels of interferon (IFN)-α2 were significantly increased by CQ treatment.
  
  
  CONCLUSIONS
  CQ was well tolerated in patients with low CD4 T-cell counts despite long-term effective ART; however, 24 weeks of CQ treatment did not improved CD4 T-cell recovery, lymphoid and myeloid immune activation or inflammatory markers.
authors.affiliation: Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada; Research Institute of McGill University Health Centre, Montreal, QC, Canada; Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: J-P
authors.initials: JP
authors.lastname: Routy
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
authors.forename: M
authors.initials: M
authors.lastname: Patel
authors.forename: C
authors.initials: C
authors.lastname: Kanagaratham
authors.forename: D
authors.initials: D
authors.lastname: Radzioch
authors.forename: I
authors.initials: I
authors.lastname: Kema
authors.forename: N
authors.initials: N
authors.lastname: Gilmore
authors.forename: P
authors.initials: P
authors.lastname: Ancuta
authors.forename: J
authors.initials: J
authors.lastname: Singer
authors.forename: M-A
authors.initials: MA
authors.lastname: Jenabian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D002097:C-Reactive Protein; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002738:Chloroquine / Q000276:immunology* / Q000627:therapeutic use; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D005338:Fibrin Fibrinogen Degradation Products; D051193:Toll-Like Receptors; C036309:fibrin fragment D; D002738:Chloroquine; D002097:C-Reactive Protein
keywords: CD4 T-cell recovery; HIV; Toll-like receptors; antiretroviral therapy; chloroquine