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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Eron, JJ; Gulick, RM; Bartlett, JA; Merigan, T; Arduino, R; Kilby, JM; Yangco, B; Diers, A; Drobnes, C; DeMasi, R; Greenberg, M; Melby, T; Raskino, C; Rusnak, P; Zhang, Y; Spence, R; Miralles, GD

Published Date

  • March 15, 2004

Published In

Volume / Issue

  • 189 / 6

Start / End Page

  • 1075 - 1083

PubMed ID

  • 14999611

Pubmed Central ID

  • 14999611

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1086/381707

Language

  • eng

Conference Location

  • United States