Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study.

TitleMemantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study.
Publication TypeJournal Article
Year of Publication2007
AuthorsSchifitto G, Navia BA, Yiannoutsos CT, Marra CM, Chang L, Ernst T, Jarvik JG, Miller EN, Singer EJ, Ellis RJ, Kolson DL, Simpson D, Nath A, Berger J, Shriver SL, Millar LL, Colquhoun D, Lenkinski R, R Gonzalez G, Lipton SA
Corporate AuthorsAdult AIDS Clinical Trial Group(ACTG) 301, 700 Teams, HIV MRS Consortium
JournalAIDS
Volume21
Issue14
Pagination1877-86
Date Published2007 Sep 12
ISSN0269-9370
KeywordsAdult, Anti-Retroviral Agents, Brain, Cognition Disorders, Double-Blind Method, Drug Therapy, Combination, Excitatory Amino Acid Antagonists, Female, HIV Infections, Humans, Magnetic Resonance Spectroscopy, Male, Memantine, Middle Aged, Neuropsychological Tests, RNA, Viral, Treatment Outcome
Abstract

OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment.

METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects.

RESULTS: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023).

CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.

DOI10.1097/QAD.0b013e32813384e8
Alternate JournalAIDS
PubMed ID17721095
Grant List5M01 RR00044 / RR / NCRR NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
R01NS34626 / NS / NINDS NIH HHS / United States
R01NS38834 / NS / NINDS NIH HHS / United States
R01RR13213 / RR / NCRR NIH HHS / United States