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: 6115864
• 负责人: Martin H Markowitz
• 金额: $ 4.54万
• 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/6115864
• 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; ritonavir; 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.

我们的小组最近报告了在我们的一系列20例患者中，使用蛋白酶抑制剂利托那韦（ABT-538）治疗的病毒载量平均降低2.1 log，剂量范围为每日600 mg至1200 mg。 反应的持久性似乎与剂量相关。 其他人最近提供的数据同样令人鼓舞，在接受600 mg BID治疗的患者中观察到最持久的反应。 因此，我们选择了最有效的药物-齐多夫定（AZT）和拉米夫定（3 TC）和利托那韦-来治疗急性感染者，宿主具有最少的遗传多样性，因此最不可能窝藏多重耐药病毒。 我们认为，病毒载量减少4到5个对数，然后出现免疫反应，应该会大大改变HIV-1感染的自然史。利托那韦（ABT-538）将在第1天以300 mg口服BID给药，第2天和第3天以400 mg口服BID给药，第4天以500 mg口服BID给药，第5天和随后以600 mg口服BID给药，前提是患者能够耐受剂量递增且无重度恶心和/或呕吐。 如果需要，可以延迟剂量递增。 AZT将以200 mg每日三次口服给药，3 TC以150 mg每日两次口服给药。 病毒学研究将包括血浆RNA测定、HIV-1的定量血浆和细胞培养以及患者PBMC的定量DNA PCR。 此外，将频繁监测T细胞亚群，以使用流式细胞术技术评估细胞隔室中的病毒载量。 还将进行药代动力学研究。