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

我们小组最近报道，在我们的20名患者中，每天服用蛋白酶抑制剂利托那韦(ABT-538)的剂量范围为600毫克至1200毫克的患者的病毒载量平均减少了2.1log。反应的持久性似乎与剂量有关。其他人最近公布的数据也同样令人鼓舞，接受600 mg Bid治疗的患者出现了最持久的反应。因此，我们选择了可用的最有效的药物--齐多夫定(AZT)、拉米夫定(3TC)和利托那韦--用于治疗急性感染者，即遗传多样性最小的宿主，因此也是最不可能存在多重耐药病毒的患者。我们建议，实现病毒载量减少4到5个对数，然后出现免疫反应，应该会极大地改变HIV-1感染的自然历史。利托那韦(ABT-538)将在第1天口服300毫克，第2天和第3天口服400毫克，第4天口服500毫克，第5天口服600毫克，前提是患者可以耐受剂量增加而没有严重恶心和/或呕吐。如果需要，剂量升级可能会被推迟。AZT口服200 mg，tid，3TC口服150 mg，2次/d。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上的定量DNA PCR。此外，将使用流式细胞仪技术对T细胞亚群进行频繁监测，以评估细胞内的病毒载量。还将进行药代动力学研究。

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.