Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: Results from a multicentre randomized clinical study

J. P. Routy*, C. L. Tremblay, J. B. Angel, B. Trottier, D. Rouleau, J. G. Baril, M. Harris, S. Trottier, J. Singer, N. Chomont, R. P. Sékaly, M. R. Boulassel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Objectives: 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 500mg 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.

Original languageEnglish
Pages (from-to)291-296
Number of pages6
JournalHIV Medicine
Volume13
Issue number5
DOIs
Publication statusPublished - May 2012

Keywords

  • CD4 T cells
  • Highly active antiretroviral therapy
  • HIV
  • Reservoir
  • Valproic acid

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

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