The purpose of this study is to examine whether the co-administration of valproic acid (Epival®), with highly active antiretroviral therapy (HAART) can reduce the size of HIV latent reservoirs in infected CD4 cells.
Participants must be on HAART with a suppressed viral load (\< 50 copies/ml) for at least the previous 12 months. They will be randomly assigned to one of two groups, one group will start the valproic acid right away at week 1 for 16 weeks, and the other group will wait until week 17 to add valproic acid to their treatment for 32 weeks. Subjects will be followed every four weeks for one year and evaluated by a variety of assays, all carried out using well-established methods, to assess the main outcome defined by changes in HIV reservoir size measured by the mean frequency of resting CD4 memory cells carrying HIV proviral DNA.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Oral valproic acid twice daily for 16 or 32 weeks. Dosage varies based on plasma levels.
As per standard of care.
BC St-Paul's Hospital/Immunodeficiency Clinic
Vancouver, British Columbia, Canada
Ottawa Health Research Institute/Immunodeficiency Clinic
Ottawa, Ontario, Canada
Actuel Medical Clinic
Montreal, Quebec, Canada
Quartier Latin Medical Clinic
Montreal, Quebec, Canada
To assess the effect of VPA on HIV reservoirs measured by the frequency of resting CD4+ memory cells carrying HIV proviral DNA in peripheral blood of chronically HIV-infected subjects.
Time frame: 16 or 32 weeks
To assess the clinical and biological tolerance of VPA in chronically HIV-infected patients with undetectable viral load.
Time frame: 16 or 32 weeks
To explore the changes in CD4/CD8 ratio, as the size of reservoir is thought to be inversely correlated with the frequency of resting CD4+ memory cells carrying HIV proviral DNA.
Time frame: 48 weeks
To explore the frequency of CD4+ memory cell subsets (Tcm, Tpm and Tem) carrying HIV proviral DNA.
Time frame: 48 weeks
To explore level of T-cell activation after VPA intervention.
Time frame: 48 weeks
To assess levels of certain cytokines and chemokines, which are involved in T-cell proliferation and differentiation.
Time frame: 48 weeks
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Montreal Chest Institute/Immunodeficiency Clinic
Montreal, Quebec, Canada
CHUL Ste-Foy
Ste-Foy, Quebec, Canada