Jabs Douglas A, Martin Barbara K, Forman Michael S, Hubbard Larry, Dunn J P, Kempen John H, Davis Janet L, Weinberg David V
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Ophthalmol. 2003 Jan;135(1):26-34. doi: 10.1016/s0002-9394(02)01759-2.
To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes.
Prospective cohort study.
Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or = 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0 micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes.
One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all < or = .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P =.012 to.021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P =.009 to.096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction.
The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.
评估在血液或尿液中检测到的对更昔洛韦耐药的巨细胞病毒是否与不良眼部结局相关。
前瞻性队列研究。
患有巨细胞病毒感染和艾滋病的患者被纳入一项关于耐药巨细胞病毒的发生及其临床相关因素的研究。在视网膜病变诊断时、治疗开始后1个月和3个月以及此后每3个月进行巨细胞病毒的血液和尿液培养。患者每月就诊一次，此时获取眼底照片并转送至眼底照片阅读中心，以评估视网膜病变进展情况（巨细胞病毒病变边界移动≥750微米，或出现新病变且面积≥0.25视盘面积）以及受巨细胞病毒性视网膜炎影响的视网膜面积。使用对数视力表测量视力。对更昔洛韦的表型耐药定义为IC50＞6.0微摩尔/升，对更昔洛韦的基因型耐药定义为出现已知赋予更昔洛韦耐药性的巨细胞病毒UL97基因突变。进行了时间依赖性分析，将病毒耐药性、高效抗逆转录病毒治疗和治疗变量作为临床结局的预测因素。
197例患者接受了更昔洛韦治疗。19例患者出现对更昔洛韦的表型耐药，18例出现基因型耐药。根据耐药的定义和所分析的培养来源，在血液或尿液中检测到对更昔洛韦耐药的巨细胞病毒与视网膜病变进展几率增加4.17至5.61倍相关（P值均≤0.0002）。耐药与3个月期间巨细胞病毒累及的视网膜面积增加幅度更大相关（1.10%对0.05%至0.10%），这在表型耐药以及血液或尿液中的基因型耐药方面具有统计学意义（P = 0.012至0.021）。有迹象表明耐药与视力丧失幅度更大相关（P = 0.009至0.096）。高效抗逆转录病毒治疗与视网膜病变进展几率降低约50%相关，更昔洛韦植入物与降低约60%相关。
在患有巨细胞病毒性视网膜炎的患者的血液或尿液中检测到对更昔洛韦耐药的巨细胞病毒与不良眼部结局风险增加相关。
