Bowen E F, Wilson P, Cope A, Sabin C, Griffiths P, Davey C, Johnson M, Emery V
Department of Virology, Royal Free Hospital and School of Medicine, London, UK.
AIDS. 1996 Nov;10(13):1515-20. doi: 10.1097/00002030-199611000-00009.
Despite life-long maintenance therapy, cytomegalovirus (CMV) retinitis frequently progresses in patients with AIDS. Virological markers that could clarify pathogenesis and identify risk factors for progression are required.
We prospectively recruited 45 patients with CMV retinitis. Blood and urine samples were collected before and after induction therapy, and on a monthly basis thereafter during routine medical and ophthalmological assessment, and at any time retinitis progressed. CMV load was measured by quantitative-competitive polymerase chain reaction (PCR).
The median time to first progression of retinitis was 78 days and to death was 8.7 months. Eighty-five per cent of patients who were PCR-positive at diagnosis of retinitis became PCR-negative after 21 days of ganciclovir induction therapy. Six patients who remained PCR-positive after 21 days of treatment had a significantly higher CMV load at presentation (P = 0.005), and a shorter time to first progression of retinitis of 40 days. High CMV loads in blood at presentation were associated with a shorter time to progression (P = 0.16; relative hazard, 1.57) and a significantly shorter time to death (P = 0.004; relative hazard, 1.76). This significant relationship with survival remained after adjustment for potential confounding variables (CD4 count, age, method of drug administration).
We conclude that CMV load in the blood of AIDS patients is an important factor in the pathogenesis of retinitis, and quantification of CMV could be used to both select patients for controlled clinical trials and to optimize individual anti-CMV induction therapy.
尽管进行了终身维持治疗,但巨细胞病毒(CMV)视网膜炎在艾滋病患者中仍经常进展。需要能够阐明发病机制并识别进展危险因素的病毒学标志物。
我们前瞻性招募了45例CMV视网膜炎患者。在诱导治疗前后、此后每月进行常规医学和眼科评估时以及视网膜炎进展的任何时候采集血液和尿液样本。通过定量竞争聚合酶链反应(PCR)测量CMV载量。
视网膜炎首次进展的中位时间为78天,死亡的中位时间为8.7个月。在视网膜炎诊断时PCR阳性的患者中,85%在更昔洛韦诱导治疗21天后变为PCR阴性。在治疗21天后仍为PCR阳性的6例患者在就诊时的CMV载量显著更高(P = 0.005),视网膜炎首次进展的时间更短,为40天。就诊时血液中高CMV载量与进展时间较短相关(P = 0.16;相对风险,1.57),与死亡时间显著缩短相关(P = 0.004;相对风险,1.76)。在对潜在混杂变量(CD4细胞计数、年龄、给药方法)进行调整后,这种与生存的显著关系仍然存在。
我们得出结论,艾滋病患者血液中的CMV载量是视网膜炎发病机制中的一个重要因素,CMV定量可用于选择患者进行对照临床试验以及优化个体抗CMV诱导治疗。