Selegiline transdermal system (STS) for HIV-associated cognitive impairment: open-label report of ACTG 5090.

TitleSelegiline transdermal system (STS) for HIV-associated cognitive impairment: open-label report of ACTG 5090.
Publication TypeJournal Article
Year of Publication2007
AuthorsEvans SR, Yeh T-min, Sacktor N, Clifford DB, Simpson D, Miller EN, Ellis RJ, Valcour V, Marra CM, Millar L, Schifitto G
Corporate AuthorsAIDS Clinical Trials Group and the Neurologic AIDS Research Consortium
JournalHIV Clin Trials
Volume8
Issue6
Pagination437-46
Date Published2007 Nov-Dec
ISSN1528-4336
KeywordsAdministration, Cutaneous, Adult, Cognition Disorders, Female, HIV Infections, Humans, Male, Middle Aged, Neuropsychological Tests, Selegiline
Abstract

OBJECTIVE: To assess the long-term safety (primary aim) and efficacy (secondary aim) of the MAO-B inhibitor Selegiline Transdermal System (STS) for the treatment of HIV-associated cognitive impairment.

BACKGROUND: HIV infection is associated with increased oxidative stress. In vitro and animal studies have shown that selegiline can reduce oxidative stress levels while enhancing the synthesis of neurotrophic factors. We conducted and reported a 24-week, double-blind, placebo-controlled study with STS in HIV-infected individuals with cognitive impairment (ACTG 5090). We now report the results of the 24-week open-label follow-up.

METHOD: Subjects received either 3 mg/24 h or 6 mg/24 h STS daily. The primary efficacy endpoint was changes in the mean of z scores of six neuropsychological tests (NPZ-6). Additional outcomes included NPZ-8 and NPZ scores by cognitive domain.

RESULTS: 86 subjects were enrolled. There were few severe adverse experiences (n = 13). There was no significant change in NPZ-6 score, whereas significant changes were observed in NPZ-8 score and several cognitive domains.

CONCLUSION: Long-term use of selegiline was safe and well tolerated in this HIV cohort of HIV with cognitive impairment. Cognitive improvement may be delayed in neuroprotective trials, suggesting that trials longer than 6 months may be necessary to assess the efficacy of putative neuroprotective agents.

DOI10.1310/hct0806-437
Alternate JournalHIV Clin Trials
PubMed ID18042509
Grant List2 U01 NS0322228-08A1 / NS / NINDS NIH HHS / United States
5-M01-RR-00722 / RR / NCRR NIH HHS / United States
AA69495 / AA / NIAAA NIH HHS / United States
AI038855 / AI / NIAID NIH HHS / United States
AI06863 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI27658 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27660 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27668 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI46376 / AI / NIAID NIH HHS / United States
AI46381 / AI / NIAID NIH HHS / United States
AI46386 / AI / NIAID NIH HHS / United States
AI69423 / AI / NIAID NIH HHS / United States
AI69424 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
AI69434 / AI / NIAID NIH HHS / United States
AI69465 / AI / NIAID NIH HHS / United States
AI69467 / AI / NIAID NIH HHS / United States
AI69470 / AI / NIAID NIH HHS / United States
AI69471 / AI / NIAID NIH HHS / United States
AI69472 / AI / NIAID NIH HHS / United States
AI69494 / AI / NIAID NIH HHS / United States
AI69495 / AI / NIAID NIH HHS / United States
AI69511 / AI / NIAID NIH HHS / United States
MH64409 / MH / NIMH NIH HHS / United States
RR00044 / RR / NCRR NIH HHS / United States
U01-AI-35040 / AI / NIAID NIH HHS / United States
U01-AI-35041 / AI / NIAID NIH HHS / United States
U01-AI-35042 / AI / NIAID NIH HHS / United States
U01-AI-35043 / AI / NIAID NIH HHS / United States
U01-AI-37613 / AI / NIAID NIH HHS / United States
U01-AI-37984 / AI / NIAID NIH HHS / United States