van 't Wout A B, Ran L J, Nijhuis M, Tijnagel J M, de Groot T, van Leeuwen R, Boucher C A, Schuitemaker H, Schuurman R
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
AIDS. 1998 Jul 9;12(10):1169-76. doi: 10.1097/00002030-199810000-00009.
To determine the effect of lamivudine (3TC) on syncytium-inducing (SI) and non-SI (NSI) HIV-1 populations in vivo.
Responses in virus load and 3TC resistance in 40 3TC-treated subjects were analysed in relation to the presence or absence of SI HIV-1 variants.
Peripheral blood samples were collected at regular intervals from 40 HIV-1-infected subjects during 3TC treatment. Virus isolates obtained at the start of treatment were typed for SI-capacity by coculture with MT-2 cells. Changes in levels of viral RNA in plasma were determined by quantitative reverse transcriptase PCR. The relative amount of wild-type and mutant virus at codon 184, associated with HIV resistance to 3TC, was determined using a primer-guided nucleotide incorporation assay after amplification of part of the reverse transcriptase gene. In five subjects the frequency of productively infected CD4+ cells with SI or NSI variants was determined in relation to codon 184 genotype.
Twenty-six subjects harboured only NSI variants at baseline, whereas 14 subjects also harboured SI variants. Although baseline plasma viral RNA load and CD4 cell counts were different between the two groups, no differences in the response to 3TC therapy were observed for these parameters. In-depth analysis of five subjects showed that the kinetics of virus load changes and emergence of 3TC resistance mutations were similar in plasma and cells, and comparable for the SI and NSI populations present in one individual.
These data show that, in contrast to didanosine and zidovudine, the pressure exerted by 3TC is similar for SI and NSI M184 populations.
确定拉米夫定（3TC）对体内诱导融合型（SI）和非诱导融合型（NSI）HIV-1群体的影响。
分析40例接受3TC治疗的受试者的病毒载量反应和3TC耐药性与SI HIV-1变异体存在与否的关系。
在3TC治疗期间，定期从40例HIV-1感染受试者采集外周血样本。治疗开始时获得的病毒分离株通过与MT-2细胞共培养来确定其SI能力类型。通过定量逆转录酶PCR测定血浆中病毒RNA水平的变化。在扩增部分逆转录酶基因后，使用引物引导的核苷酸掺入试验确定与HIV对3TC耐药相关的密码子184处野生型和突变型病毒的相对量。在5名受试者中，确定了产生SI或NSI变异体的有 productive感染的CD4+细胞频率与密码子184基因型的关系。
26名受试者在基线时仅携带NSI变异体，而14名受试者也携带SI变异体。尽管两组之间基线血浆病毒RNA载量和CD4细胞计数不同，但这些参数在对3TC治疗的反应中未观察到差异。对5名受试者的深入分析表明，血浆和细胞中病毒载量变化的动力学以及3TC耐药突变的出现相似，并且在个体中存在的SI和NSI群体具有可比性。
这些数据表明，与去羟肌苷和齐多夫定不同，3TC对SI和NSI M184群体施加的压力相似。
