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

我们的研究小组最近报道，在我们的20例患者中，使用蛋白酶抑制剂利托那韦（ABT-538）每日600毫克至1200毫克的剂量范围治疗，病毒载量平均降低了2.1 logs。反应的持久性似乎与剂量有关。最近其他人提供的数据同样令人鼓舞，在接受600mg BID治疗的患者中看到了最持久的反应。因此，我们选择了最有效的药物——齐多夫定（AZT）、拉米夫定（3TC）和利托那韦——来治疗急性感染者，这是遗传多样性最少的宿主，因此也是最不可能携带多重耐药病毒的宿主。我们提出，实现病毒载量的4 - 5个对数的减少，然后免疫反应的出现，应该会极大地改变HIV-1感染的自然史。利托那韦（ABT-538）将在第1400天口服BID为300 mg，第2天口服BID为400 mg，第4天口服BID为3500 mg，第5天口服BID为600 mg，并随后给予，前提是患者能够耐受剂量增加而无严重恶心和/或呕吐。如有必要，剂量的增加可以推迟。AZT口服剂量为200mg TID， 3TC口服剂量为150mg BID。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，将使用流式细胞术频繁监测t细胞亚群，以评估细胞室中的病毒载量。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.