title: Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.
abstract: BACKGROUND
  Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms.
  
  
  OBJECTIVE
  To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment.
  
  
  METHODS
  This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared.
  
  
  RESULTS
  There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test).
  
  
  CONCLUSIONS
  Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles 90033, USA.
authors.forename: P N
authors.initials: PN
authors.lastname: Heseltine
authors.forename: K
authors.initials: K
authors.lastname: Goodkin
authors.forename: J H
authors.initials: JH
authors.lastname: Atkinson
authors.forename: B
authors.initials: B
authors.lastname: Vitiello
authors.forename: J
authors.initials: J
authors.lastname: Rochon
authors.forename: R K
authors.initials: RK
authors.lastname: Heaton
authors.forename: E M
authors.initials: EM
authors.lastname: Eaton
authors.forename: F L
authors.initials: FL
authors.lastname: Wilkie
authors.forename: E
authors.initials: E
authors.lastname: Sobel
authors.forename: S J
authors.initials: SJ
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Feaster
authors.forename: L
authors.initials: L
authors.lastname: Schneider
authors.forename: W L
authors.initials: WL
authors.lastname: Goldschmidts
authors.forename: E S
authors.initials: ES
authors.lastname: Stover
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000276:immunology; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015717:Peptide T / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015717:Peptide T