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Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV ‐1 reservoirs: results from a multicentre randomized clinical study
Author(s) -
Routy JP,
Tremblay CL,
Angel JB,
Trottier B,
Rouleau D,
Baril JG,
Harris M,
Trottier S,
Singer J,
Chomont N,
Sékaly RP,
Boulassel MR
Publication year - 2012
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2011.00975.x
Subject(s) - medicine , antiretroviral therapy , valproic acid , randomized controlled trial , therapeutic index , human immunodeficiency virus (hiv) , viral load , gastroenterology , immunology , pharmacology , drug , epilepsy , psychiatry
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 CD 4 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 CD 4 T cells at baseline and at weeks 16 and 48. Results No significant reductions in the frequency of CD 4 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.