Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV
Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV
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DOI：
10.1086/381707
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发表时间：
2004-03-15
影响因子：
6.4
通讯作者：
Miralles, GD
中科院分区：
文献类型：
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作者：
Eron, JJ;Gulick, RM;Miralles, GD
T-1249是一种由39个氨基酸组成的合成肽，可抑制人类免疫缺陷病毒（HIV）与宿主靶细胞的融合。在115名HIV-1感染成人中进行了一项为期14天的开放标签、I/II期剂量递增单药治疗研究，以评估T-1249的安全性和抗逆转录病毒活性。在基线时，大多数患者患有晚期HIV疾病（基线中位CD 4（+）细胞计数，57个细胞/穆尔），并接受了广泛的预治疗（即，T-1249前）抗逆转录病毒药物治疗经验（中位数，11种抗逆转录病毒药物）。患者接受皮下注射T-1249单药治疗，持续14天，剂量范围为6.25 - 192 mg/天。T-1249通常耐受良好，未发现剂量限制性毒性。注射部位反应是最常报告的不良事件（57%）。观察到血浆HIV-1 RNA载量呈剂量依赖性降低;各剂量组较基线的中位最大变化范围为-0.29 log（10）拷贝/mL（95%置信区间[CI]，-0.43至-0.05 log（10）拷贝/mL），最低剂量为-1.96 log（10）拷贝/mL（95% CI，-2.02至-1.37拷贝/mL）。这些结果表明T-1249是一种有效的治疗HIV-1感染的新药物。
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/muL) 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.