Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV. Academic Article uri icon

Overview

abstract

  • T-1249 is a 39-aa synthetic peptide that inhibits fusion of human immunodeficiency virus (HIV) to the host target cell. A 14-day open-label, phase 1/2 dose-escalation monotherapy study of the safety and antiretroviral activity of T-1249 was performed on 115 HIV-1-infected adults. At baseline, the majority of the patients had advanced HIV disease (baseline median CD4(+) cell count, 57 cells/microL) and had extensive pretreatment (i.e., pre-T-1249) experience with antiretroviral medications (median, 11 antiretroviral drugs). Patients received T-1249 monotherapy by subcutaneous injection, for 14 days, at doses ranging from 6.25 to 192 mg/day. T-1249 was generally well tolerated, and no dose-limiting toxicity was identified. Injection-site reactions were the most commonly reported adverse event (57%). Dose-dependent decreases in plasma HIV-1 RNA load were observed; the median maximum change from baseline across dose groups ranged from -0.29 log(10) copies/mL (95% confidence interval [CI], -0.43 to -0.05 log(10) copies/mL) for the lowest dose to -1.96 log(10) copies/mL (95% CI, -2.02 to -1.37 copies/mL) for the highest dose. These results indicate that T-1249 is a potent new therapeutic agent for HIV-1 infection.

authors

  • Eron, Joseph J
  • Gulick, Roy M
  • Bartlett, John A
  • Merigan, Thomas
  • Arduino, Roberto
  • Kilby, J Michael
  • Yangco, Bienvenido
  • Diers, Adriann
  • Drobnes, Claude
  • DeMasi, Ralph
  • Greenberg, Michael
  • Melby, Thomas
  • Raskino, Claire
  • Rusnak, Pam
  • Zhang, Ying
  • Spence, Rebecca
  • Miralles, G Diego

publication date

  • March 2, 2004

Research

keywords

  • Acquired Immunodeficiency Syndrome
  • Anti-HIV Agents
  • HIV Envelope Protein gp41
  • HIV-1
  • Peptide Fragments

Identity

Scopus Document Identifier

  • 12144290487

Digital Object Identifier (DOI)

  • 10.1086/381707

PubMed ID

  • 14999611

Additional Document Info

volume

  • 189

issue

  • 6