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


CONCLUSIONS
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.
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Nancy M
NM
Archin
Joseph J
JJ
Eron
Sarah
S
Palmer
Anne
A
Hartmann-Duff
Jeffery A
JA
Martinson
Ann
A
Wiegand
Nicholas
N
Bandarenko
John L
JL
Schmitz
Ronald J
RJ
Bosch
Alan L
AL
Landay
John M
JM
Coffin
David M
DM
Margolis
D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D014635:Valproic Acid / Q000627:therapeutic use*; D014766:Viremia / Q000517:prevention & control
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D012367:RNA, Viral; D014635:Valproic Acid