Once-Daily Drug Regimen for HIV-Infected Patients

Overview

This study will examine the safety of giving antiviral therapy for HIV infection in a once-daily dosing schedule, and assess how well patients tolerate this regimen. A once a day dosing schedule may be easier for some people to follow than one that requires taking medicine 2 or 3 times a day. The ease of treatment is important, because not following the prescribed dosing regimen may make therapy less effective or ineffective. HIV-infected patients 18 years and older who have never been treated for their infection may be eligible for this study. Candidates will be screened with a history and physical examination, including blood tests. Participants will take the following medications once a day: 1200 mg of amprenavir (8 capsules); 300 mg of ritonavir (3 capsules); 600 mg of abacavir (2 pills); and 300 mg of lamivudine (2 pills). Patients will have routine blood tests and be seen by a nurse or doctor, or both, at follow-up visits at weeks 2, 4, 8, 12, and 16; then every 8 weeks until week 48; and then every 3 months for up to 3 years. At week 2, a special blood test will be done over the course of a day to measure blood drug levels. For this test, blood samples will be drawn 8 times over a 24-hour period. A heparin lock (a device that allows the needle to remain in the vein) will be used to avoid multiple needle sticks.

The development of a once-daily anti-retroviral regimen is a priority because regimen simplicity might enhance regimen adherence, and because a once-daily regimen would be useful for directly observed therapy. Pharmacokinetic modeling suggests that plasma levels of amprenavir in the presence of ritonavir, a potent inhibitor of cytochrome p450, should be high enough to support once-daily dosing. Lamivudine is currently being explored in other studies in once-daily dosing. Abacavir has not been used once daily but some in vitro studies suggest that such dosing might be appropriate. In this uncontrolled, open-label study, amprenavir 1200 mg daily, ritonavir 300 mg daily, lamivudine 300 mg daily, and abacavir 600 mg daily will be administered to up to 25 HIV-infected, anti-retroviral naive patients. The objectives are to assess the tolerability and safety of this regimen; the plasma concentrations of amprenavir; and the anti-viral response. Study evaluations include percentage of patients who have discontinued the regimen by weeks 16 and 24 for toxicity, intolerance or failure; the number of grade 3 and 4 adverse events by weeks 16 and 24; the antiviral response at weeks 16, 24, and 48 (change from baseline and percentage of patients with viral load less than 50 copies and less than 400 copies per mL), and the number (percent) of patients with trough plasma concentrations of amprenavir above 280 ng/mL.