Valproic acid is associated with cognitive decline in HIV-infected individuals: a clinical observational study

BACKGROUND: Valproic acid (VPA) is often used to control pain in HIV-related neuropathy. However, the effect of VPA on cognitive functions in advanced HIV-infected individuals is largely unknown. A recent study would suggest that it may have a neuroprotective effect, the doses used were low and the observation period short. METHODS: We used a well studied HIV-infected cohort assessed for a median of 15 (range 6–27 months) to determine whether individuals who were receiving VPA showed any cognitive benefits. Multiple regression procedures allowed us to control for the effects of HAART and HIV disease status as well as numbers of visits and variation in VPA intake over-time. RESULTS: We found a negative effect of VPA (mean dose of 850 mg/d for 18 months on average; range 6–27 months) on cognitive performance in eight advanced HIV-infected individuals compared to 32 advanced HIV-infected individuals on no VPA who had comparable neuropsychological performance at baseline. Control for plasma HIV viral load provided similar results. CONCLUSION: Our results suggest that further studies of VPA in advanced HIV-infection should cautiously include high doses over prolonged periods of at least 18 months in order to more accurately determine whether the posited neuroprotective benefit of VPA still occurs or whether it is replaced by toxicity.