Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells

Nancy M. Archin, Joseph J. Eron, Sarah Palmer, Anne Hartmann-Duff, Jeffery A. Martinson, Ann Wiegand, Nicholas Bandarenko, John L. Schmitz, Ronald J. Bosch, Alan L. Landay, John M. Coffin, David M. Margolis

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Objectives:: Valproic acid and intensified antiretroviral therapy may deplete resting CD4+ T-cell HIV infection. We tested the ability of valproic acid to deplete resting CD4+ T-cell infection in patients receiving standard antiretroviral therapy. Methods:: Resting CD4+ T-cell infection was measured in 11 stably aviremic volunteers twice prior to, and twice after Depakote ER 1000 mg was added to standard antiretroviral therapy. Resting CD4+ T-cell infection frequency was measured by outgrowth assay. Low-level viremia was quantitated by single copy plasma HIV RNA assay. Results:: A decrease in resting CD4+ T-cell infection was observed in only four of the 11 patients. Levels of immune activation and HIV-specific T-cell response were low and stable. Valproic acid levels ranged from 26 to 96 μg/ml when measured near trough. Single copy assay was performed in nine patients. In three patients with depletion of resting CD4+ T-cell infection following valproic acid, single copy assay ranged from less than 1-5 copies/ml. Continuous low-level viremia was observed in three patients with stable resting CD4+ T-cell infection (24-87, 8-87, and 1-7 copies/ml respectively) in whom multiple samples were analyzed. Conclusion:: The prospective addition of valproic acid to stable antiretroviral therapy reduced the frequency of resting CD4+ T-cell infection in a minority of volunteers. In patients in whom resting CD4+ T-cell infection depletion was observed, viremia was rarely detectable by single copy assay.

Original languageEnglish (US)
Pages (from-to)1131-1135
Number of pages5
JournalAIDS
Volume22
Issue number10
DOIs
StatePublished - Jun 19 2008
Externally publishedYes

Keywords

  • Antiretroviral therapy
  • HIV
  • Latency
  • Resting CD4+ T cells
  • Valproic acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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