Safety and Effectiveness of the Selegiline "Patch" for Decreased Mental Function in HIV Patients

• Change in cognitive performance Week 24 from screening
  
• frequencies of adverse experiences, abnormal results on laboratory tests, changes over time in laboratory tests and vital signs
  

• Clinical global impression by the investigator comparing selegiline-treated arms with the placebo arm
  
• clinical global impression by the subject comparing selegiline-treated arms with the placebo arm
  
• cognitive domain-specific scores compared between selegiline-treated arms and the placebo arm
  
• neuropsychologic function tests (NPZ-8)
  
• fatigue scale (quality of life)
  
• markers of immune activation and oxidative stress/apoptosis
  
• comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to cognitive performance
  
• comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to historical data in normal volunteers after 7 days of transdermal selegiline administration
  
• comparison of selegiline and active metabolite steady-state concentrations at Week 4 in subjects on ritonavir-containing protease inhibitor (PI) antiviral regimens, subjects on other PI regimens, and subjects on non-PI-containing antiviral regimens
  

Cognitive impairment is a common adverse effect of HIV infection that can progress to dementia. ARVs are the only current therapy, but treatment response is frequently unsatisfactory, short lived, or the agents are poorly tolerated in doses adequate for central nervous system (CNS) penetration. An adjunctive therapy that interferes with the cascade of events triggered by the virus is likely to play an important role. Oral selegiline is an approved and marketed drug for the symptomatic treatment of Parkinson's disease. Studies suggest that selegiline has a neuroprotective effect and that it may exert a "rescue effect" on dying and injured neurons. This study proposes to use transdermal selegiline, which may deliver a greater dose level than oral administration, in the treatment of HIV-associated cognitive impairment.

This is a two-step study, with each step lasting 24 weeks. Step 1 is double-blind and Step 2 is open label. At entry, patients are randomly assigned to receive either the STS or placebo. One STS patch will be applied daily at the same time for 24 weeks. Patients are evaluated at the clinic at entry and at Weeks 2, 4, 8, 12, 16, and 24. Cognitive status will be evaluated by performance on a series of neuropsychological assessments. Patients who complete Step 1 may participate in Step 2. Patients on placebo in Step 1 will receive active STS treatment in Step 2. The STS patch is applied once daily for an additional 24 weeks and patients are evaluated at the clinic at Weeks 28, 36, and 48.