Kilby J M, Hopkins S, Venetta T M, DiMassimo B, Cloud G A, Lee J Y, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson M R, Nowak M A, Shaw G M, Saag M S
Department of Medicine, University of Alabama at Birmingham, 35294-2050, USA.
Nat Med. 1998 Nov;4(11):1302-7. doi: 10.1038/3293.
T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.
T-20是一种与HIV-1包膜蛋白跨膜亚基区域相对应的合成肽，在体外浓度低于2 ng/ml时可阻断细胞融合和病毒进入。我们对四个剂量组（每日两次，剂量分别为3、10、30和100 mg）的16名HIV感染成人静脉注射T-20（单一疗法），持续14天。所有接受较高剂量水平的受试者血浆HIV RNA均出现了与剂量相关的显著下降。通过bDNA检测，所有四名每日两次接受100 mg剂量的受试者血浆HIV RNA均降至低于500拷贝/ml。一种灵敏的RT-PCR检测法（检测阈值为40拷贝/ml）表明，尽管在14天给药期内未达到检测不到的水平，但这些受试者血浆HIV RNA的中位数下降了1.96 log10。本研究提供了病毒进入在体内可被成功阻断的概念验证。短期给予T-20似乎是安全的，并能提供与目前批准的抗逆转录病毒方案相当的对HIV复制的有效抑制。
