Chun T W, Stuyver L, Mizell S B, Ehler L A, Mican J A, Baseler M, Lloyd A L, Nowak M A, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.
Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals receiving such treatment. The present study demonstrates that highly purified CD4+ T cells from 13 of 13 patients receiving HAART with an average treatment time of 10 months and with undetectable (<500 copies HIV RNA/ml) plasma viremia by a commonly used bDNA assay carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro. Phenotypic analysis of HIV-1 produced by activation of latently infected CD4+ T cells revealed the presence in some patients of syncytium-inducing virus. In addition, the presence of unintegrated HIV-1 DNA in infected resting CD4+ T cells from patients receiving HAART, even those with undetectable plasma viremia, suggests persistent active virus replication in vivo.
虽然以包括蛋白酶抑制剂在内的三联药物组合形式的高效抗逆转录病毒疗法（HAART）能够将一些HIV-1感染个体的血浆病毒载量降低到检测不到的水平，但尚不清楚这些治疗方案对潜伏感染的CD4+ T细胞有何影响，以及这些细胞在接受此类治疗的个体中HIV-1感染的持续存在中发挥何种作用。本研究表明，13例接受HAART治疗的患者，平均治疗时间为10个月，通过常用的分支DNA检测法检测到血浆病毒血症不可检测（<500拷贝HIV RNA/ml），其高度纯化的CD4+ T细胞携带整合的前病毒DNA，并且在体外细胞活化后能够产生传染性病毒。对潜伏感染的CD4+ T细胞活化产生的HIV-1进行表型分析，发现在一些患者中存在诱导合胞体病毒。此外，接受HAART治疗的患者，即使是血浆病毒血症检测不到的患者，其感染的静息CD4+ T细胞中存在未整合的HIV-1 DNA，这表明体内存在持续的活跃病毒复制。
