Shire N J, Welge J A, Sherman K E
Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH 45267, USA.
J Viral Hepat. 2007 Apr;14(4):239-48. doi: 10.1111/j.1365-2893.2006.00824.x.
Several recent trials have determined varying rates of response to pegylated interferon plus ribavirin (peg-IFN + RIB) in hepatitis C virus (HCV)/human immunodeficiency virus-coinfected patients. We sought to identify a pooled response rate and sources of interstudy variability. A literature search was conducted to identify randomized or prospective studies evaluating response rates to peg-IFN + RIB in coinfected patients. A Bayesian hierarchical model was used to estimate overall response rate. Between-study variance was calculated and sensitivity analyses were conducted. Meta-regression was employed to identify sources of between-study variability. The literature search yielded seven studies of 146, which matched keywords and inclusion criteria. The combined patient total was 784. Individual intention-to-treat response rates ranged from 27.3% to 44.2%. The pooled Bayesian estimate of percent response was 33.3%. Significant interstudy heterogeneity was detected. Meta-regression yielded no significant effects of covariates on response rate. Subanalyses by CD4+, HCV viral load and genotype yielded sustained virological response (SVR) odds ratios of 0.73 for low CD4+, 0.41 for high viral load and 0.30 for genotype 1/4. The pooled response rate is not attributable to any one study. Response is poor compared with HCV-monoinfected patients. Interstudy variability is not satisfactorily explained by factors influencing individual response, but may be due to differences between studies unavailable for inclusion in this analysis. However, both genotype 1/4 and high HCV viral load at baseline were significantly associated with a reduction in odds of SVR in pooled subanalysis. Improved treatments are needed in coinfected patients, especially with genotype 1/4 and high viral load.
最近的几项试验已确定丙型肝炎病毒(HCV)/人类免疫缺陷病毒合并感染患者对聚乙二醇化干扰素加利巴韦林(peg-IFN + RIB)的反应率各不相同。我们试图确定合并反应率以及研究间变异性的来源。进行了文献检索,以确定评估合并感染患者对peg-IFN + RIB反应率的随机或前瞻性研究。使用贝叶斯分层模型估计总体反应率。计算研究间方差并进行敏感性分析。采用Meta回归确定研究间变异性的来源。文献检索产生了7项针对146名患者的研究,这些研究符合关键词和纳入标准。患者总数为784名。个体意向性治疗反应率范围为27.3%至44.2%。合并的贝叶斯反应率估计值为33.3%。检测到显著的研究间异质性。Meta回归显示协变量对反应率无显著影响。按CD4 +、HCV病毒载量和基因型进行的亚分析得出,低CD4 +时持续病毒学应答(SVR)优势比为0.73,高病毒载量时为0.41,基因型1/4时为0.30。合并反应率并非归因于任何一项研究。与HCV单感染患者相比,反应较差。影响个体反应的因素不能令人满意地解释研究间变异性,但可能是由于本分析中未纳入的研究之间的差异所致。然而,在合并亚分析中,基因型1/4和基线时高HCV病毒载量均与SVR几率降低显著相关。合并感染患者需要改进治疗方法,尤其是基因型1/4和病毒载量高的患者。