Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment

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. Patients and 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 0.200x 10⁹/L (200 cells/μL) 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 X² 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 ≤0.5) or with relatively preserved immunological status (ie, CD4⁺ cell count >0.200X 10⁹/L).