Objective: To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment.
Background: The results of a 20-week, randomized, double-blind, placebo-controlled trial of memantine in HIV-infected participants with cognitive impairment (ACTG 301) were previously reported. We report the results of the up-to-60-week open-label phase following the double-blind phase.
Method: Participants received open-label memantine and were escalated to a 40 mg/day dose or their maximum tolerated dose in the double- blind phase. Adverse experiences were used to evaluate safety, and changes in the mean of eight neuropsychological test scores (NPZ-8) were used to evaluate efficacy.
Results: Ninety-nine participants entered the initial 12-week open-label phase and 45 in the additional 48-week extension. Twenty-seven participants reported severe adverse experiences. During the initial 12-week open-label phase, participants randomized to memantine in the double-blind phase had a statistically significant higher improvement in NPZ-8 compared to those randomized to placebo in the double-blind phase. No statistically significant NPZ-8 changes were detected during the 48-week extension.
Conclusion: Long-term use of memantine appears safe and tolerable. Future randomized studies with longer follow-up are necessary to establish efficacy of memantine for the treatment of HIV-associated cognitive impairment.
Trial registration: ClinicalTrials.gov NCT00000867.