CTN 205: Valproic acid and HIV

About The Study

The purpose of this study was 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 were randomly assigned to one of two groups, one group began taking the valproic acid right away at week 1 for 16 weeks, and the other group waited until week 17 to add valproic acid to their treatment for 32 weeks.

This study enrolled 50 participants at several Canadian sites, and lasted 48 weeks.

Study Approach

The study was open to HIV-positive male and female patients who had been on HAART with a suppressed viral load (< 50 co/ml) for at least 12 months before study onset.

Results

Eighty-four per cent of participants were male with a mean CD4 and nadir CD4 of 537 and 200 respectively. The 2 groups did not differ in nadir CD4 or baseline CD4 cell counts, pre ART viral load, or duration of aviremia on ART. Of the 56 patients, 12 failed to complete the study protocol, 2 discontinued due to SAE’s, and 8 discontinued the study due to VPA adverse events. In the group receiving VPA in the first 16 weeks, 38.1% (8/21) had a significant reduction compared to 38.9% (7/18) the control arm (Fisher’s exact p= 0.99). Comparing the HIV reservoir between the end of the control period and the end of the VPA treatment period it was found for the 39 patients that, 16 had a significant reduction on VPA compared to the control group, 14 had a significant reduction on control compared to VPA, and 9 had smaller differences between the two periods of treatment.

Conclusions

Valproic acid is a relatively safe treatment for HIV-infected patients; however neither 16 nor 32 weeks of therapy showed any signs of a significant impact on the HIV reservoir.