Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for clinical trials in organ transplant recipients. Viral load may be a more relevant endpoint due to low frequency of disease. We performed a meta-analysis and systematic review of the literature. We found several lines of evidence to support the validity of viral load as an appropriate surrogate end-point, including the following: (1) viral loads in CMV disease are significantly greater than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6–19.3); (2) kinetics of viral replication are strongly associated with progression to disease; (3) pooled incidence of CMV viremia and disease is significantly lower during prophylaxis compared with the full patient follow-up period (viremia incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001); (4) treatment of viremia prevented disease; and (5) viral load decline correlated with symptom resolution. Based on the analysis, we conclude that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients.

中文翻译：

---

在实体器官移植中巨细胞病毒临床研究中使用病毒载量作为替代指标：系统评价和荟萃分析

有症状的巨细胞病毒（CMV）疾病已成为器官移植接受者临床试验的标准终点。由于疾病的发生频率较低，病毒载量可能是一个更相关的终点。我们对文献进行了荟萃分析和系统回顾。我们发现了几条证据支持病毒载量作为适当的替代终点的有效性，包括以下几点：（1）CMV疾病中的病毒载量显着大于无症状病毒血症（优势比，9.3 95％置信区间， 4.6–19.3）；（2）病毒复制的动力学与疾病的发展密切相关；（3）与整个患者随访期相比，预防期间CMV病毒血症和疾病的合并发生率明显更低（病毒血症发生率：3.2％vs 34.3％；P<.001）（疾病发生率：1.1％对13.0％；P <.001）；（4）病毒血症预防疾病的治疗；（5）病毒载量下降与症状缓解相关。根据分析，我们得出结论，对于器官移植接受者中的CMV试验，CMV负荷是合适的替代终点。