Relative anti-HIV-1 efficacy of lamivudine and emtricitabine in vitro is dependent on cell type
Relative anti-HIV-1 efficacy of lamivudine and emtricitabine in vitro is dependent on cell type
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DOI：
10.1097/00126334-200303010-00003
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发表时间：
2003-03-01
影响因子：
3.6
通讯作者：
Lanier, ER
中科院分区：
文献类型：
--
作者：
Hazen, R;Lanier, ER
目的：评估抗病毒药物恩曲他滨（FTC）、拉米夫定（3 TC）和齐多夫定（ZDV）在感染HIV-1的外周血单核细胞（PBMC）、单核细胞衍生的巨噬细胞和MT-4细胞中的相对体外效力。设计：供试化合物抗HIV-1嗜M性或嗜T性实验室菌株和抗抗逆转录病毒治疗的临床HIV-1分离株的体外评价-方法：基于50%抑制浓度使用碘化丙啶染色宿主细胞DNA评估细胞病变效应或测量HIV-1逆转录酶活性评估病毒复制抑制的抗病毒效力的标准方法。在HIV-1（IIIB）感染的PBMC或HIV-1（Ba-L）感染的单核细胞衍生巨噬细胞（体内HIV-1感染的主要细胞类型）的试验中，3 TC和FTC之间的效价无显著差异。与早期的报道一致，在HIV-1（IIIB）感染的转化T细胞系MT-4中，FTC的活性约为3 TC的四倍，而ZDV的活性高于FTC。3 TC、FTC和ZDV对来自PBMC中抗逆转录病毒初治受试者的一组8株主要HIV-1分离株具有同等活性。这些结果证明了原代细胞中3 TC和FTC活性的体外相似性。效力的变异性取决于细胞类型和病毒株强调了我们的观察，即体外抗病毒作用不是体内临床活性的可靠预测因子。
Objective: To assess the relative in vitro potency of the antiviral agents emtricitabine (FTC), lamivudine (3TC), and zidovudine (ZDV) in peripheral blood mononuclear cells (PBMCs), monocyte-derived macrophages, and MT-4 cells infected with HIV-1.Design: In vitro evaluation of the test compounds against M-tropic or T-tropic laboratory strains of HIV-1 and against clinical HIV-1 isolates from antiretroviral therapy-naive subjects using PBMCs, monocyte-derived macrophages, and MT-4 cells.Methods: Standard methods for assessing antiviral potency based on 50% inhibitory concentrations using propidium iodide staining of host cell DNA to assess cytopathic effects or measurement of HIV-1 reverse transcriptase activity to assess inhibition of viral replication.Results: There were no significant differences in potency between 3TC and FTC in assays with HIV-1(IIIB)-infected PBMCs or HIV-1(Ba-L)-infected monocyte-derived macrophages, which are primary cell types for HIV-1 infection in vivo. In agreement with earlier reports, FTC was approximately fourfold more active than 3TC in assays in the transformed T-cell line MT-4 infected with HIV-1(IIIB), whereas ZDV was more active than FTC. 3TC, FTC, and ZDV were equally active against a panel of eight primary HIV-1 isolates from antiretroviral-naive subjects in PBMCs. These results demonstrate the in vitro similarity of 3TC and FTC activity in primary cells. The variability in potency depending on cell types and viral strains underscores our observation that antiviral effects in vitro are not reliable predictors of in vivo clinical activity.