Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of d-Ala₁-peptide T-amide for HIV-1-associated cognitive-motor impairment

Abstract

D-Ala₁-peptide T-amide (DAPTA) has shown neuroprotection in vitro against gp120-induced loss of dendritic arborization and is promulgated as a CCR5 antagonist. A multisite, randomized, double-blind clinical trial of DAPTA versus placebo prior to combination antiretroviral therapy conducted with human immunodeficiency virus (HIV)-1 seropositive participants having cognitive impairment showed no overall cognitive effect, though subgroups with greater impairment and CD4 cell counts of 201 to 500 cells/mm³ at baseline showed significant improvement. The objective of this study was to examine whether intranasal administration of DAPTA at a dose of 2 mg three times per day (tid) was associated with a reduction of cerebrospinal fluid (CSF) and peripheral (plasma and serum) viral load among a subgroup of participants completing 6 months of treatment. Baseline and 6-month CSF (n = 92) and peripheral (plasma n = 33; serum n = 24) viral load were measured by the Roche Ultrasensitive assay, version 1.5, with reflexive use of the AMPLICOR assay and preservation of the blind. A DAPTA treatment indicator variable was tested using generalized linear models on change in viral load. Peripheral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group. No group differences in CSF viral load were found. This retrospective study on a limited subgroup of the original trial sample indicated that DAPTA treatment may reduce peripheral viral load without concomitant CSF effects. Future studies should be undertaken to confirm the existence of this result and the CSF-periphery dissociation observed with respect to HIV-1–associated cognitive-motor impairment. Journal of NeuroVirology (2006) 12, 178–189.

• Keywords
• CSF
• clinical trial
• cognition
• DAPTA
• HIV
• peptide T
• viral load

This research was funded through NIMH contracts to the University of Miami (N01MH20004; PI: Karl Goodkin, MD, PhD), University of Southern California (N01MH00013; PI: Peter N. R. Heseltine, MD), and University of California San Diego (N01MH20007; PI: J. Hampton Atkinson, MD). The authors acknowledge Steven A. Herman, PhD, Senior Research Leader, Roche Molecular Systems, for his support in provision of the kits used and in the design and interpretation of the assay validation study. The authors would also like to acknowledge James W. Bremer, PhD, and Cheryl Jennings of Rush Medical College, Chicago, IL, and Donald Brambilla, PhD, of New England Research Institutes, Inc., Watertown, MA, for their support in the conduct and interpretation of the assay validation study using CSF and plasma. In addition the authors wish to recognize Walter Scott, PhD, of the University of Miami School of Medicine for his support in participating as a site in the validation study and Xuguang Guo of Constella Health Sciences for conducting the statistical analyses. The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services.