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

Division of Hematology, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada.
HIV Medicine (Impact Factor: 3.99). 01/2012; 13(5):291-6. DOI: 10.1111/j.1468-1293.2011.00975.x
Source: PubMed


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.
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.
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.
Our study demonstrates that adding VPA to stable HAART does not reduce the latent HIV reservoir in virally suppressed patients.

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Available from: Joel Singer, Jan 04, 2016
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