This work was presented in part at the 17th Conference on Retroviruses and Opportunistic Infections (CROI), 16–19 February 2010, San Francisco, CA, USA.
Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study†
Article first published online: 26 JAN 2012
© 2012 British HIV Association
Volume 13, Issue 5, pages 291–296, May 2012
How to Cite
Routy, J., Tremblay, C., Angel, J., Trottier, B., Rouleau, D., Baril, J., Harris, M., Trottier, S., Singer, J., Chomont, N., Sékaly, R. and Boulassel, M. (2012), Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study. HIV Medicine, 13: 291–296. doi: 10.1111/j.1468-1293.2011.00975.x
- Issue published online: 1 APR 2012
- Article first published online: 26 JAN 2012
- Manuscript Accepted: 7 OCT 2011
- American Foundation. Grant Number: amfAR#106722-40RGRL
- Canadian Foundation. Grant Number: CANFAR #017-718
- CIHR Canadian HIV Trials Network. Grant Number: CTN 205
- Abbott Canada
- CD4 T cells;
- highly active antiretroviral therapy;
- valproic acid
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 log10 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.