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


METHODS
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.


CONCLUSIONS
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.
Evans
Scott R
SR
Harvard School of Public Health, Boston, Massachusetts, USA.
Yeh
Tzu-Min
TM
Sacktor
Ned
N
Clifford
David B
DB
Simpson
David
D
Miller
Eric N
EN
Ellis
Ronald J
RJ
Valcour
Victor
V
Marra
Christina M
CM
Millar
Linda
L
Schifitto
Giovanni
G
D000279:Administration, Cutaneous; D000328:Adult; D003072:Cognition Disorders / Q000188:drug therapy*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D012642:Selegiline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D012642:Selegiline