Nielsen C, Gøtzsche P C, Nielsen C M, Gerstoft J, Vestergaard B F
Department of Virology, Statens Seruminstitut (SSI), Copenhagen, Denmark.
Antiviral Res. 1992 Jun;18(3-4):303-16. doi: 10.1016/0166-3542(92)90063-b.
An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected 'in vitro' with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.
建立了一种基于用无细胞病毒“体外”感染的CD4 +淋巴细胞培养物中HIV抗原产生的检测方法。使用该检测方法，尽管细胞嗜性和诱导合胞体能力存在差异，但仍有可能从所有患者中分离、增殖并可靠地确定HIV分离株对齐多夫定的敏感性。使用该检测方法，研究了16例患者在开始治疗前后获得的52株连续分离株的齐多夫定敏感性差异。早在开始治疗4个月后，就从13例患者中分离出对齐多夫定敏感性降低10至100倍的HIV。齐多夫定治疗的月数与病毒耐药性的发展密切相关，高CD4细胞计数往往与较低的耐药性发展率相关。从CD4 +淋巴细胞和血浆中同时获得的分离株之间的敏感性差异，以及从CD4 +淋巴细胞克隆中分离的病毒株之间的敏感性差异，证实了患者可携带对齐多夫定敏感性不同的病毒株混合物。
