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
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA.
J Infect Dis. 2004 Jan 15;189(2):286-91. doi: 10.1086/380802. Epub 2004 Jan 8.
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.
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.
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.
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.
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。
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。
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。
单剂量TNX - 355可降低HIV感染受试者的血浆HIV - 1 RNA载量并增加CD4 + T细胞计数。其治疗潜力的进一步评估有待更长疗程试验的数据。
