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

NM Archin, JJ Eron, S Palmer, A Hartmann-Duff… - Aids, 2008 - journals.lww.com
NM Archin, JJ Eron, S Palmer, A Hartmann-Duff, JA Martinson, A Wiegand, N Bandarenko…
Aids, 2008journals.lww.com
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 …
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.
Lippincott Williams & Wilkins