Kozal M J, Shafer R W, Winters M A, Katzenstein D A, Aguiniga E, Halpern J, Merigan T C
Center for AIDS Research, Stanford University Medical Center, California 94305.
J Acquir Immune Defic Syndr (1988). 1994 Aug;7(8):832-8.
The variable rate of disease progression in HIV-1-infected patients treated with zidovudine may be related to certain viral characteristics, such as, antiviral drug resistance, virus burden, and viral syncytium-inducing (SI) capacity. Thirty-two HIV-1-infected patients treated with zidovudine (mean of 34 months) were studied to determine the relationship of SI phenotype and the codon 215 pol gene mutation (a marker of zidovudine resistance) to virus burden and CD4 cell decline. Patients with SI strains and the codon 215 mutation in their proviral DNA had a 54% decline in CD4 cells and a virus burden of 21,480 proviral DNA copies/10(6) CD4 cells. In contrast, patients with non-SI (NSI) strains and wild-type at codon 215 had a 10% increase in CD4 cells and had a viral burden 1/46 that of patients with SI and the 215 mutation. Among patients with NSI strains, changes in CD4 cells depended on the presence of the codon 215 mutation (-160 CD4 cells/microliters), compared with those wild-type at codon 215 (+28 CD4 cells/microliters) (p < 0.01). There was a concordant rise in virus burden between proviral DNA and plasma HIV RNA depending on HIV phenotype and genotype. Using multiple linear regression, SI phenotype and the codon 215 mutation were found to independently predict CD4 cell decline and increased virus burden in zidovudine-treated patients.
接受齐多夫定治疗的HIV-1感染患者疾病进展速度各异，这可能与某些病毒特征有关，如抗病毒药物耐药性、病毒载量和病毒诱导合胞体（SI）的能力。对32名接受齐多夫定治疗（平均34个月）的HIV-1感染患者进行了研究，以确定SI表型和pol基因215密码子突变（齐多夫定耐药性的一个标志物）与病毒载量和CD4细胞减少之间的关系。前病毒DNA中具有SI毒株和215密码子突变的患者，其CD4细胞减少了54%，病毒载量为21,480个前病毒DNA拷贝/10(6)个CD4细胞。相比之下，具有非SI（NSI）毒株且215密码子为野生型的患者，其CD4细胞增加了10%，病毒载量是具有SI和215突变患者的1/46。在具有NSI毒株的患者中，CD4细胞的变化取决于215密码子突变的存在情况（-160个CD4细胞/微升），而215密码子为野生型的患者则为（+28个CD4细胞/微升）（p < 0.01）。根据HIV表型和基因型，前病毒DNA和血浆HIV RNA中的病毒载量呈一致上升。通过多元线性回归发现，SI表型和215密码子突变可独立预测接受齐多夫定治疗患者的CD4细胞减少和病毒载量增加。
