人类嗜T淋巴细胞病毒1型对逆转录酶抑制剂的敏感性：对拉米夫定耐药的证据。

Susceptibility of human T cell leukemia virus type 1 to reverse-transcriptase inhibitors: evidence for resistance to lamivudine.

作者信息

García-Lerma J G, Nidtha S, Heneine W

机构信息

HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.

出版信息

J Infect Dis. 2001 Aug 15;184(4):507-10. doi: 10.1086/322785. Epub 2001 Jul 25.

DOI:10.1086/322785

PMID:11471110

Abstract

Nucleoside reverse-transcriptase (RT) inhibitors (NRTIs), including lamivudine (3TC) and zidovudine (Zdv), are being evaluated for the treatment of human T cell lymphotropic virus type 1 (HTLV-1)-associated disease. However, information on the susceptibility of HTLV-1 to these drugs is limited. The activity of 5 NRTIs on HTLV-1 RT was evaluated. IC(50) values for Zdv, zalcitabine (ddC), didanosine (ddI), 3TC, and stavudine (d4T) were determined, using an enzymatic assay, for 5 HTLV-1 isolates and for reference wild-type and NRTI-resistant human immunodeficiency virus type 1 (HIV-1). Both HTLV-1 and wild-type HIV-1 were equally susceptible to Zdv, ddC, ddI, and d4T. In contrast, high-level resistance to 3TC was found in all HTLV-1 isolates. The findings support the clinical use of Zdv, ddC, ddI, and d4T but not of 3TC for the antiretroviral treatment of HTLV-1-associated disease.

摘要

核苷逆转录酶（RT）抑制剂，包括拉米夫定（3TC）和齐多夫定（Zdv），正在被评估用于治疗人类嗜T淋巴细胞病毒1型（HTLV-1）相关疾病。然而，关于HTLV-1对这些药物敏感性的信息有限。评估了5种核苷逆转录酶抑制剂对HTLV-1逆转录酶的活性。使用酶法测定了5株HTLV-1分离株以及参考野生型和耐核苷逆转录酶抑制剂的人类免疫缺陷病毒1型（HIV-1）对Zdv、扎西他滨（ddC）、去羟肌苷（ddI）、3TC和司他夫定（d4T）的半数抑制浓度（IC50）值。HTLV-1和野生型HIV-1对Zdv、ddC、ddI和d4T的敏感性相同。相反，在所有HTLV-1分离株中均发现对3TC的高水平耐药。这些发现支持将Zdv、ddC、ddI和d4T用于HTLV-1相关疾病的抗逆转录病毒治疗，但不支持使用3TC。