Wainberg M A, Drosopoulos W C, Salomon H, Hsu M, Borkow G, Parniak M, Gu Z, Song Q, Manne J, Islam S, Castriota G, Prasad V R
McGill AIDS Centre, Jewish General Hospital, Montreal, Canada.
Science. 1996 Mar 1;271(5253):1282-5. doi: 10.1126/science.271.5253.1282.
Monotherapy with (-)2',3'-dideoxy-3'-thiacytidine (3TC) leads to the appearance of a drug-resistant variant of human immunodeficiency virus-type 1 (HIV-1) with the methionine-184 --> valine (M184V) substitution in the reverse transcriptase (RT). Despite resulting drug resistance, treatment for more than 48 weeks is associated with a lower plasma viral burden than that at baseline. Studies to investigate this apparent contradiction revealed the following. (i) Titers of HIV-neutralizing antibodies remained stable in 3TC-treated individuals in contrast to rapid declines in those treated with azidothymidine (AZT). (ii) Unlike wild-type HIV, growth of M184V HIV in cell culture in the presence of d4T, AZT, Nevirapine, Delavirdine, or Saquinavir did not select for variants displaying drug resistance. (iii) There was an increase in fidelity of nucleotide insertion by the M184V mutant compared with wild-type enzyme.
用（-）2'，3'-二脱氧-3'-硫代胞苷（3TC）进行单一疗法会导致出现一种对人免疫缺陷病毒1型（HIV-1）具有耐药性的变体，其逆转录酶（RT）中存在甲硫氨酸184→缬氨酸（M184V）替换。尽管产生了耐药性，但超过48周的治疗与基线时相比，血浆病毒载量较低。旨在研究这一明显矛盾现象的研究揭示了以下几点。（i）与用叠氮胸苷（AZT）治疗的个体中HIV中和抗体滴度迅速下降不同，在接受3TC治疗的个体中，HIV中和抗体滴度保持稳定。（ii）与野生型HIV不同，在细胞培养中，M184V HIV在存在司他夫定（d4T）、AZT、奈韦拉平、地拉韦定或沙奎那韦的情况下生长，不会选择出显示耐药性的变体。（iii）与野生型酶相比，M184V突变体的核苷酸插入保真度有所提高。
