Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.
OBJECTIVE
To assess the safety and tolerability of lexipafant in HIV-associated cognitive impairment.


BACKGROUND
Cognitive impairment is the most common neurologic complication of advanced HIV-1 infection. There is evidence that a variety of inflammatory mediators, including platelet-activating factor (PAF), may contribute to neuronal injury. We hypothesized that lexipafant, a PAF antagonist, might improve cognitive dysfunction in HIV-infected people.


METHODS
We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the safety and tolerability of lexipafant 500 mg/day. The primary outcome measure for tolerability was the ability to complete the study on the originally assigned dosage of medication. Thirty patients with cognitive impairment were enrolled.


RESULTS
Lexipafant was safe and well tolerated. Ninety-three percent in the placebo group and 88% in the lexipafant group completed the study at the originally assigned dosage. Trends toward improvement were seen in neuropsychological performance, especially verbal memory, in the lexipafant treatment group.


CONCLUSIONS
This study shows that lexipafant, the first PAF antagonist used in HIV-associated cognitive impairment, is a safe and well tolerated compound. The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance.
Schifitto
G
G
University of Rochester Medical Center, NY, USA.
Sacktor
N
N
Marder
K
K
McDermott
M P
MP
McArthur
J C
JC
Kieburtz
K
K
Small
S
S
Epstein
L G
LG
D000328:Adult; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology / Q000821:virology*; D004311:Double-Blind Method; D005260:Female; D006678:HIV; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007930:Leucine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D010972:Platelet Activating Factor; D007930:Leucine; C103289:lexipafant