抗CD4单克隆抗体TNX-355对1型HIV感染患者的抗逆转录病毒活性。

Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1.

作者信息

Kuritzkes Daniel R, Jacobson Jeffrey, Powderly William G, Godofsky Eliot, DeJesus Edwin, Haas Frances, Reimann Keith A, Larson Jeffrey L, Yarbough Patrice O, Curt Valentin, Shanahan William R

机构信息

Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA.

出版信息

J Infect Dis. 2004 Jan 15;189(2):286-91. doi: 10.1086/380802. Epub 2004 Jan 8.

DOI:10.1086/380802

PMID:14722894

Abstract

BACKGROUND

We wished to determine the safety and anti-human immunodeficiency virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4 monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected subjects.

METHODS

Sequential cohorts of 6 HIV-1-infected subjects each received infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4+ T cell count, TNX-355 coating of CD4+ T cells, and serum TNX-355 levels.

RESULTS

Dose-related reductions in plasma HIV-1 RNA loads correlated with complete CD4+ T cell coating by TNX-355. Peak median decreases in plasma HIV-1 RNA loads were 0.56, 1.33, and 1.11 log10 copies/mL and occurred on days 4-7, 14, and 21 for the 3.0, 10, and 25 mg/kg doses, respectively. Dose-dependent increases in CD4+ T cell count occurred within 24 h of dosing.

CONCLUSIONS

Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4+ T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.

摘要

背景

我们希望确定单剂量TNX - 355（一种在体外对HIV - 1具有强效活性的人源化IgG4抗CD4单克隆抗体）在HIV感染受试者中的安全性及抗人类免疫缺陷病毒1型（HIV - 1）活性。

方法

每组6名HIV - 1感染受试者的连续队列接受TNX - 355输注。数据包括血浆HIV - 1 RNA水平、CD4 + T细胞计数、TNX - 355对CD4 + T细胞的包被情况以及血清TNX - 355水平。

结果

血浆HIV - 1 RNA载量的剂量相关降低与TNX - 355对CD4 + T细胞的完全包被相关。血浆HIV - 1 RNA载量的峰值中位数下降分别为0.56、1.33和1.11 log10拷贝/毫升，分别在3.0、10和25 mg/kg剂量组的第4 - 7天、第14天和第21天出现。给药后24小时内出现剂量依赖性的CD4 + T细胞计数增加。