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

HIV Med. 2012 May;13(5):291-6. doi: 10.1111/j.1468-1293.2011.00975.x. Epub 2012 Jan 26.

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 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.

Trial registration: ClinicalTrials.gov NCT00289952.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / virology*
  • Cross-Over Studies
  • Drug Therapy, Combination / methods
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Valproic Acid / therapeutic use*
  • Viral Load
  • Virus Latency / drug effects*

Substances

  • Enzyme Inhibitors
  • Valproic Acid

Associated data

  • ClinicalTrials.gov/NCT00289952