COMBINATION THERAPY RITONAVIR (ABT 538), LAMIVUDINE AND ZIDOVUDINE IN HIV

利托那韦 (ABT 538)、拉米夫定和齐多夫定联合治疗 HIV

• 批准号: 6277098
• 负责人: Martin H Markowitz
• 金额: $ 5.84万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277098
• 关键词: AIDS therapy; HIV infections; antiAIDS agent; antiviral agents; clinical research; clinical trials; combination chemotherapy; drug screening /evaluation; human subject; human therapy evaluation; lamivudine; zidovudine

Our group has recently reported a mean reduction in viral load of 2.1 logs in our series of 20 patients treated with the protease inhibitor ritonavir (ABT-538) in a dose range of 600 mg to 1200 mg daily. Durability of response appears to be dose related. Data recently presented by others were equally encouraging, with the most durable responses seen in the patients treated with 600 mg BID. Therefore, we have chosen the most active drugs available -- zidovudine (AZT) and lamivudine (3TC) and ritonavir -- to treat the acutely infected person, the host with the least genetic diversity, and therefore the one least likely to harbor multiply resistant viruses. We propose that achieving a four-to-five-log reduction in viral load, which would then be followed by the appearance of the immune response, should dramatically alter the natural history of HIV-1 infection. Ritonavir (ABT-538) will be administered at 300 mg orally BID on Day 1, 400 mg orally BID on days 2 and 3, 500 mg orally BID on day 4, and 600 mg orally BID on Day 5 and subsequently, provided the patient can tolerate the dose escalation without severe nausea and/or vomiting. If needed, the dose escalations may be delayed. AZT will be administered at 200 mg orally TID, and 3TC at 150 mg orally BID. Virologic studies will include plasma RNA determinations, quantitative plasma and cell culture for HIV-1, and quantitative DNA PCR on patient PBMC. In addition, frequent monitoring of T-cell subsets will be performed to assess the viral load in the cellular compartment using flow cytometric techniques. Pharmacokinetic studies will also be performed.

我们小组最近报告说，病毒载量平均减少了2.1个对数 在我们的一系列20名患者中，使用了蛋白酶抑制剂利托那韦 (ABT-538)，剂量范围为每天600毫克至1200毫克。的耐用性 反应似乎与剂量有关。其他人最近提供的数据 同样令人鼓舞，最持久的反应出现在 患者服用600 mg，2次/d。因此，我们选择了最多的 可用的活性药物-齐多夫定(AZT)和拉米夫定(3TC)和 利托那韦--用最少的药物治疗急性感染者 基因多样性，因此是最不可能繁衍的 抗药性病毒。我们建议实现四到五个对数的减少 病毒载量，紧随其后的是出现 免疫反应，应该极大地改变HIV-1的自然历史 感染。利托那韦(ABT-538)300毫克，每日2次口服 第1天口服400毫克，第2天口服，第4天口服3500毫克， 在第五天口服600毫克，随后，如果患者能 耐受剂量增加，不会出现严重的恶心和/或呕吐。如果 如果需要，剂量升级可能会推迟。AZT将在 TID 200 mg，3TC，150 mg，2次/d。病毒学研究将 包括血浆RNA测定、定量血浆和细胞培养 用于HIV-1，以及患者PBMC上的定量DNA PCR。此外, 将对T细胞亚群进行频繁监测，以评估 用流式细胞仪技术检测细胞内的病毒载量。 还将进行药代动力学研究。