TREATMENT OF CHRONIC HEPATITIS B VIRUS INFECTION

慢性乙型肝炎病毒感染的治疗

• 批准号: 3768882
• 负责人: S E STRAUS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3768882
• 关键词: HIV infections; antiviral agents; cytomegalovirus; dosage; drug adverse effect; drug screening /evaluation; hepatitis B; hepatitis B virus group; human subject; human therapy evaluation; liver disorder chemotherapy; microorganism disease chemotherapy

We have been exploring the potential antiviral efficacy of a class of fluoropyrimidine nucleoside analogues. Initially we explored the drug FIAC for inhibition of CMV infection in AIDS patients. Antiviral activity was not seen at tolerated doses and studies turned to this drug's metabolic derivative, FIAU. Studies showed intolerance at high doses but excellent tolerance and profound inhibitory activity at lower doses against hepatitis B virus (HBV). The initial studies involved HIV positive patients with co-existing chronic HBV infection. Profound and even permanent reductions in circulating HBV DNA and antigens were achieved with oral FIAU at daily doses of 0.1, -.5, or 1 mg/kg for 14 days. We then turned to a broader dose modification study in normal patients with chronic HBV infection. Studies compared antiviral efficacy at .05, 0.1, 0.25 and 0.5 mg/kg per day for 28 days. We noted profound inhibition of HBV infection even at the lowest doses and in the absence of any substantial side effects. By 9 months after treatment 9 of 24 patients had lost HBV DNA; 2 of which lost HBeAg. Based on these findings 24 HIV-negative chronic HBV patients are being enrolled in a randomized study comparing 0.1 and 0.l25 mg/kg per day for 6 months to determine long term safety and efficacy.

我们一直在探索一类药物的潜在抗病毒效果 氟嘧啶核苷类似物。最初，我们探索了这种药物 FIAC用于抑制艾滋病患者巨细胞病毒感染。抗病毒药物 在耐受剂量下没有观察到活性，研究转向了这一点 药物的代谢衍生物，FIAU。研究表明不耐受程度很高 剂量，但在较低的剂量下具有良好的耐受性和深刻的抑制活性 抗乙肝病毒(乙肝)的剂量。最初的研究涉及艾滋病毒 慢性乙肝病毒感染阳性的患者。深刻而深刻 甚至循环中的HBVDNA和抗原的永久性减少也是 口服FIAU，每天0.1、-.5或1 mg/kg，共14次 几天。然后，我们转向了一项更广泛的剂量调整研究 慢性乙肝病毒感染者。比较抗病毒疗效的研究 每天0.05、0.1、0.25和0.5 mg/kg，共28天。我们注意到深刻的 即使在最低剂量和不存在的情况下也能抑制乙肝病毒感染 任何实质性的副作用。治疗后9个月24人中有9人 2例HBVDNA丢失，其中2例HBeAg丢失。基于这些 结果24名HIV阴性的慢性乙肝患者正在参加一项 一项随机研究，比较了6个月内每天0.1和0.125毫克/公斤的 确定长期安全性和有效性。