Stellbrink H J, van Lunzen J, Hufert F T, Fröschle G, Wolf-Vorbeck G, Zöllner B, Albrecht H, Greten H, Racz P, Tenner-Racz K
Medical Department, Eppendorf University Hospital, Hamburg, Germany.
AIDS. 1997 Jul 15;11(9):1103-10. doi: 10.1097/00002030-199709000-00004.
To study the kinetics of plasma viraemia and HIV-infected lymph-node cells in stable asymptomatic HIV infection with high CD4+ T-cell counts.
Nine asymptomatic HIV-infected patients with stable CD4+ T-cell counts (510-1350 x 10(6)/l) were treated with a triple-drug combination. Plasma viraemia was determined at days 0, 3, 7, 10, 14, 21 and 28 of treatment [Roche polymerase chain reaction (PCR) and ultrasensitive PCR assay]. Sequential lymph-node biopsies were examined in four patients before and after 4 weeks of treatment. Productively infected cells were counted in lymph-node sections (in situ hybridization). The infection rates of FACS-sorted CD4+ lymph-node T cells and the expression of single-spliced, double-spliced and full-length HIV transcripts were determined.
HIV plasma RNA half-lives ranged from 1.4 to 2.7 days. Viral turnover varied between 0.07 and 7.54 x 10(8) copies per day. The number of productively infected lymph-node cells as well as the amount of extracellular virus in germinal centres was markedly reduced during treatment, paralleled by a clearance of single-spliced, double-spliced and full-length HIV transcripts from CD4+ lymph-node T cells. Plasma viraemia remained detectable with an ultrasensitive PCR assay in three out of four patients. The percentage of lymph-node CD4+ T cells harbouring proviral DNA decreased only slightly.
The kinetics of HIV replication are rapid in stable asymptomatic infection, and the magnitude of replication varies considerably. Productively infected lymph-node cells and extracellular virus in germinal centres undergo a rapid turnover, whereas latently infected CD4+ T cells have a lower rate of turnover. The latter may contribute substantially to viral persistence during therapy.
研究在CD4+T细胞计数较高的稳定无症状HIV感染中血浆病毒血症及HIV感染淋巴结细胞的动力学。
9例CD4+T细胞计数稳定（510 - 1350×10⁶/l）的无症状HIV感染患者接受三联药物联合治疗。在治疗的第0、3、7、10、14、21和28天测定血浆病毒血症[罗氏聚合酶链反应（PCR）和超敏PCR检测]。4例患者在治疗4周前后进行连续的淋巴结活检。对淋巴结切片进行原位杂交以计数有 productive感染的细胞。测定FACS分选的淋巴结CD4+T细胞的感染率以及单剪接、双剪接和全长HIV转录本的表达。
HIV血浆RNA半衰期为1.4至2.7天。病毒周转量在每天0.07至7.54×10⁸拷贝之间变化。治疗期间，生发中心有productive感染的淋巴结细胞数量以及细胞外病毒量显著减少，同时CD4+淋巴结T细胞中的单剪接、双剪接和全长HIV转录本也被清除。4例患者中有3例通过超敏PCR检测仍可检测到血浆病毒血症。携带前病毒DNA的淋巴结CD4+T细胞百分比仅略有下降。
在稳定无症状感染中HIV复制动力学迅速，且复制程度差异很大。生发中心有productive感染的淋巴结细胞和细胞外病毒周转迅速，而潜伏感染的CD4+T细胞周转速率较低。后者可能在治疗期间对病毒持续存在起重要作用。
