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

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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.