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

Karl Goodkin, Benedetto Vitiello, William D. Lyman, Deshratn Asthana, J. Hampton Atkinson, Peter N.R. Heseltine, Rebeca Molina, Wenli Zheng, Imad Khamis, Frances L. Wilkie, Paul Shapshak

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)178-189
Number of pages12
JournalJournal of neurovirology
Volume12
Issue number3
DOIs
StatePublished - Jun 1 2006

Keywords

  • Clinical trial
  • Cognition
  • CSF
  • DAPTA
  • HIV
  • Peptide T
  • Viral load

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

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    Goodkin, K., Vitiello, B., Lyman, W. D., Asthana, D., Atkinson, J. H., Heseltine, P. N. R., Molina, R., Zheng, W., Khamis, I., Wilkie, F. L., & Shapshak, P. (2006). 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. Journal of neurovirology, 12(3), 178-189. https://doi.org/10.1080/13550280600827344