Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Acquir Immune Defic Syndr. 2010 Mar;53(3):357-63. doi: 10.1097/QAI.0b013e3181c7a29d.
This study aimed to assess the relationship between interferon (IFN)-related adverse effects and Hepatitis C virus (HCV) virologic response in HIV/HCV-coinfected individuals treated with pegylated interferon and ribavirin.
We conducted 2 prospective, open-label trials treating HIV/HCV-coinfected individuals with pegylated interferon alpha-2b or alpha-2a and ribavirin for 48 weeks. Safety laboratories, HCV RNA, psychiatric, and ophthalmologic evaluations were performed at baseline and monthly until week 72.
Responders were defined as those with HCV RNA decline of > or = 2-log drop from baseline and nonresponders were those who did not. Remarkably, of the 27 patients (50%) who developed psychiatric toxicities, 26 patients were responders, although only 1 of 14 virologic nonresponders experienced psychiatric toxicity. Other adverse effects, such as anemia and ophthalmologic toxicities, were also more frequent in responders compared with nonresponders. Decline in CD4 T-cell counts strongly correlated with HCV viral decline.
Our study demonstrates coupling of antiviral effect and occurrence of adverse events in HIV/HCV-coinfected patients. These patients with IFN-related adverse effects need a multidisciplinary treatment approach, hence, they are more likely to achieve sustained virologic response. Future studies are needed to evaluate the factors that predict the development of IFN-alpha-dependent adverse events before therapy.
本研究旨在评估 HIV/HCV 合并感染个体接受聚乙二醇干扰素和利巴韦林治疗时,干扰素(IFN)相关不良反应与丙型肝炎病毒(HCV)病毒学应答之间的关系。
我们进行了两项前瞻性、开放性标签试验,对 HIV/HCV 合并感染个体使用聚乙二醇干扰素α-2b 或α-2a 和利巴韦林治疗 48 周。安全性实验室、HCV RNA、精神科和眼科评估在基线和每月进行,直到第 72 周。
应答者定义为 HCV RNA 从基线下降≥2 对数的患者,无应答者为未达到此标准的患者。值得注意的是,在发生精神毒性的 27 例患者(50%)中,26 例为应答者,尽管仅有 1 例病毒学无应答者出现精神毒性。与无应答者相比,其他不良反应,如贫血和眼科毒性,在应答者中也更为常见。CD4 T 细胞计数下降与 HCV 病毒下降强烈相关。
我们的研究表明,HIV/HCV 合并感染患者的抗病毒效果与不良反应的发生相关。这些发生 IFN 相关不良反应的患者需要多学科治疗方法,因此更有可能实现持续的病毒学应答。未来的研究需要评估治疗前预测 IFN-α 相关不良反应发生的因素。