ANTIHIV ACTIVITY OF 60MG DAILY DOSE ADEFOVIR DIFIVOXIL IN HIV INFECTED PATIENTS

每日剂量 60 毫克阿德福韦酯对 HIV 感染患者的抗 HIV 活性

• 批准号: 6297588
• 负责人: PATRICIA A BARDITCH-CROVO
• 金额: $ 0.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297588
• 关键词: AIDS; AIDS therapy; HIV infections; antiAIDS agent; clinical research; clinical trial phase I; drug adverse effect; drug interactions; drug screening /evaluation; human subject; nucleoside analog; pharmacokinetics; reverse transcriptase inhibitors

Despite the improved activity of combination antiretroviral therapies in patients with HIV infection, the antiviral, immunologic, and clinical impact of such therapies appears to be incomplete and is often transient. In addition, treatment with the agents noted above may be associated with significant drug interactions and side effects. Combination therapies with complicated administration regimens also pose a challenge to some populations requiring antiretroviral therapy. Therefore, the identification of novel and conveniently administered agents in combination strategies for treating patients with HIV infection would be of great benefit. Adefovir dipivoxil, a nucleotide reverse transcriptase inhibitor, has been shown to be effective in vivo against HIV by its ability to reduce viral load measurements including p24Ag and HIV RNA. Adefovir dipivoxil at a dose of 60 mg daily has been utilized in previous trials but only as a dose reduction from 120 mg in response to clinically significant toxicities or intolerance. Previous clinical trials have demonstrated a clear dose-dependent relationship for adefovir dipivoxil related adverse events. However, no clear dose dependence has been established for the antiviral activity of adefovir dipivoxil at the doses clinically studied: 125 mg to 500 mg daily. The antiviral activity or safety profile of adefovir dipivoxil 60 mg daily has not been examined. It is possible that a daily dose of 60 mg has the same anti-HIV effect as 125 mg. Therefore, the rationale for conducting this protocol is to determine if there is antiviral activity of adefovir dipivoxil at a lower dose than those tested previously in human trials.

尽管联合抗逆转录病毒疗法的活性有所提高， 在HIV感染患者中，抗病毒、免疫和临床 这种疗法的效果似乎是不完全的，往往是 短暂的 此外，用上述试剂的治疗可以是有效的。 与显著的药物相互作用和副作用相关。 具有复杂给药方案的联合疗法也造成了 这对一些需要抗逆转录病毒治疗的人群来说是一个挑战。 因此，新的和方便施用的鉴定 用于治疗HIV患者的组合策略中的药剂 感染会有很大的好处。 阿德福韦酯，一种核苷酸 逆转录酶抑制剂，已被证明是有效的在体内 通过其降低病毒载量测量的能力来对抗HIV，包括 p24Ag和HIV RNA。 阿德福韦酯每日60毫克的剂量已用于 之前的试验，但仅作为剂量从120 mg减少，以响应 临床显著毒性或不耐受。 既往临床 试验表明， 阿德福韦酯相关不良事件。 然而，没有明确的剂量 阿德福韦酯的抗病毒活性依赖性已被确立 临床研究剂量的地塞昔单抗：每日125 mg至500 mg。 的 阿德福韦酯每日60 mg的抗病毒活性或安全性特征 还没有被检查。 每日60 mg的剂量有可能 与125 mg相同的抗HIV效果。 因此， 进行这项研究的目的是确定是否有抗病毒活性， 阿德福韦酯的剂量低于之前测试的剂量 人体试验