title: Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial.
abstract: BACKGROUND
  Therapies to decrease immune activation might be of benefit in slowing HIV disease progression.
  
  
  OBJECTIVE
  To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL.
  
  
  METHODS
  Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks.
  
  
  METHODS
  The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models.
  
  
  RESULTS
  There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P = .80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P = .03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P = .003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P = .03).
  
  
  CONCLUSIONS
  Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN30019040.
authors: MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom. nick.paton@ctu.mrc.ac.uk
authors: Nicholas I
authors: NI
authors: Paton
authors: Ruth L
authors: RL
authors: Goodall
authors: David T
authors: DT
authors: Dunn
authors: Samuel
authors: S
authors: Franzen
authors: Yolanda
authors: Y
authors: Collaco-Moraes
authors: Brian G
authors: BG
authors: Gazzard
authors: Ian G
authors: IG
authors: Williams
authors: Martin J
authors: MJ
authors: Fisher
authors: Alan
authors: A
authors: Winston
authors: Julie
authors: J
authors: Fox
authors: Chloe
authors: C
authors: Orkin
authors: Elbushra A
authors: EA
authors: Herieka
authors: Jonathan G
authors: JG
authors: Ainsworth
authors: Frank A
authors: FA
authors: Post
authors: Mark
authors: M
authors: Wansbrough-Jones
authors: Peter
authors: P
authors: Kelleher
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D044966:Anti-Retroviral Agents; D006886:Hydroxychloroquine