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

Research output: Contribution to journalArticle

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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

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Highly Active Antiretroviral Therapy
Valproic Acid
HIV-1
HIV
T-Lymphocytes
Clinical Studies
Cross-Over Studies
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

Cite this

Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs : Results from a multicentre randomized clinical study. / Routy, J. P.; Tremblay, C. L.; Angel, J. B.; Trottier, B.; Rouleau, D.; Baril, J. G.; Harris, M.; Trottier, S.; Singer, J.; Chomont, N.; Sékaly, R. P.; Boulassel, M. R.

In: HIV Medicine, Vol. 13, No. 5, 05.2012, p. 291-296.

Research output: Contribution to journalArticle

Routy, JP, Tremblay, CL, Angel, JB, Trottier, B, Rouleau, D, Baril, JG, Harris, M, Trottier, S, Singer, J, Chomont, N, Sékaly, RP & Boulassel, MR 2012, 'Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: Results from a multicentre randomized clinical study', HIV Medicine, vol. 13, no. 5, pp. 291-296. https://doi.org/10.1111/j.1468-1293.2011.00975.x
Routy, J. P. ; Tremblay, C. L. ; Angel, J. B. ; Trottier, B. ; Rouleau, D. ; Baril, J. G. ; Harris, M. ; Trottier, S. ; Singer, J. ; Chomont, N. ; Sékaly, R. P. ; Boulassel, M. R. / Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs : Results from a multicentre randomized clinical study. In: HIV Medicine. 2012 ; Vol. 13, No. 5. pp. 291-296.
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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.",
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