Salmon-Céron D, Mazeron M C, Chaput S, Boukli N, Senechal B, Houhou N, Katlama C, Matheron S, Fillet A M, Gozlan J, Leport C, Jeantils V, Freymuth F, Costagliola D
Department of Internal Medicine, Hospital Cochin, Paris, France.
AIDS. 2000 May 26;14(8):1041-9. doi: 10.1097/00002030-200005260-00017.
To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART).
Prospective multicentre cohort in 15 university hospitals in France.
A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction).
At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l.
CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.
在高效抗逆转录病毒治疗（HAART）背景下研究巨细胞病毒（CMV）疾病的自然史及当前风险因素。
法国15家大学医院开展的前瞻性多中心队列研究。
选取198例CD4细胞计数<100×10⁶个细胞/升（或接受HAART至少2个月后<200×10⁶个细胞/升）、既往无CMV疾病且CMV血清学阳性的患者，每4个月进行临床随访及病毒学检测，包括HIV RNA和CMV血液标志物（培养、pp65抗原血症、血浆CMV DNA以及通过聚合酶链反应检测的CMV晚期mRNA）。
纳入研究时，CD4中位数为77×10⁶个细胞/升（0 - 308），85%的患者接受蛋白酶抑制剂治疗。12个月时接受HAART的患者比例达99%。经过23.6个月的随访，CMV疾病发病率为3.2/100患者年[95%置信区间（CI）1.3 - 5.0]。在单变量Cox模型中，所有CMV标志物、CD4细胞计数持续<75×10⁶个细胞/升以及HIV病毒载量>100,000拷贝/毫升均为CMV疾病的预测因素。CMV疾病的风险比分别为：血培养11；pp65抗原血症≥1个核/200,000个细胞为14，≥100个核/200,000个细胞为70；血浆CMV DNA为35；CMV mRNA为6；CD4<75×10⁶个细胞/升为29；HIV RNA>100,000拷贝/毫升为12。在逐步多变量分析中，仅三个协变量与疾病发生独立相关：血浆CMV DNA、pp65抗原血症≥100个核/200,000个细胞以及CD4计数<75×10⁶个细胞/升。
CMV血液标志物及CD4计数<75×10⁶个细胞/升仍是接受HAART患者发生CMV疾病的风险因素。通过聚合酶链反应分析血浆CMV DNA是一种可重复且标准化的工具，可作为启动CMV抢先治疗的决策标志物。
