title: Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study.
abstract: OBJECTIVE
  Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART). In a randomized multicentre, cross-over study, we assessed whether adding VPA to stable HAART could potentially reduce the size of the latent viral reservoir in CD4 T cells of chronically infected patients.
  
  
  METHODS
  A total of 56 virologically suppressed patients were randomly assigned either to receive VPA plus HAART for 16 weeks followed by HAART alone for 32 weeks (arm 1; n  = 27) or to receive HAART alone for 16 weeks and then VPA plus HAART for 32 weeks (arm 2; n  = 29). VPA was administered at a dose of 500  mg twice a day (bid) and was adjusted to the therapeutic range. A quantitative culture assay was used to assess HIV reservoirs in CD4 T cells at baseline and at weeks 16 and 48.
  
  
  RESULTS
  No significant reductions in the frequency of CD4 T cells harbouring replication-competent HIV after 16 and 32 weeks of VPA therapy were observed. In arm 1, median (range) values of IU per log(10) billion (IUPB) cells were 2.55 (range 1.20-4.20), 1.80 (range 1.0-4.70) and 2.70 (range 1.0-3.90; P = 0.87) for baseline, week 16 and week 48, respectively. In arm 2, median values of IUPB were 2.55 (range 1.20-4.65), 1.64 (range 1.0-3.94) and 2.51 (range 1.0-4.48; P = 0.50) for baseline, week 16 and week 48, respectively.
  
  
  CONCLUSIONS
  Our study demonstrates that adding VPA to stable HAART does not reduce the latent HIV reservoir in virally suppressed patients.
authors.affiliation: Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada. jean-pierre.routy@mcgill.ca
authors.forename: J P
authors.initials: JP
authors.lastname: Routy
authors.forename: C L
authors.initials: CL
authors.lastname: Tremblay
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
authors.forename: B
authors.initials: B
authors.lastname: Trottier
authors.forename: D
authors.initials: D
authors.lastname: Rouleau
authors.forename: J G
authors.initials: JG
authors.lastname: Baril
authors.forename: M
authors.initials: M
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Trottier
authors.forename: J
authors.initials: J
authors.lastname: Singer
authors.forename: N
authors.initials: N
authors.lastname: Chomont
authors.forename: R P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: M R
authors.initials: MR
authors.lastname: Boulassel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000379:methods; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014635:Valproic Acid / Q000627:therapeutic use*; D019562:Viral Load; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid