A Study of Amprenavir in Patients With Protease Inhibitor-Related Complications

Protease inhibitors are highly efficacious in the treatment of HIV-1 disease. Current drugs, however, are associated with a high incidence of adverse effects as well as metabolic complications such as lipodystrophy and hyperlipidemia. At the same time, though, a causal relationship linking these complications to the use of protease inhibitors remains to be established. Studies have shown APV to be well tolerated and effective in reducing plasma HIV-1 RNA levels. The safety profile of APV suggests it may offer therapeutic potential in subjects developing intolerance to other protease inhibitors.

Patients receive open-label APV plus at least 2 other antiretroviral drugs. Fasting blood samples and patient medication adherence questionnaires are collected at Weeks 12 and 24. Bodily assessments are collected at Day 1 and Weeks 12 and 24. Hematology, serum chemistry, plasma HIV-1 viral load determination and CD4+ cell count measurements are collected at pre-entry and every 12 weeks for the duration of the study.

Inclusion criteria

Patients must have:

• Documented HIV-1 infection.
• Two consecutive (at least 4 weeks apart) screening HIV-1 plasma RNA levels less than or equal to 10,000 copies/ml prior to open-label drug administration.
• Hyperlipidemia with or without lipodystrophy (Grade 1-4 toxicity for triglycerides or total cholesterol), be intolerant to standard protease inhibitor therapy and, in the judgment of the physician, be unable to construct a viable treatment regimen without APV.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Renal failure requiring dialysis.
• Hepatic failure.
• Serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction which, in the opinion of the investigator, would compromise the safety of the patient.
• Malabsorption syndrome or other gastrointestinal dysfunction, which might interfere with drug absorption or render the patient unable to take oral medication.

Concurrent Treatment:

Excluded:

Concomitant use of another protease inhibitor.

Patients with the following prior condition are excluded:

Clinically relevant history of pancreatitis or hepatitis within the last 6 months.

Prior Treatment:

Excluded:

Previous treatment with APV.

Risk Behavior:

Excluded:

Patients currently using alcohol or illicit drugs which, in the investigator's opinion, may interfere with the patient's ability to comply with the requirements of the study.

Included:

Prior treatment with at least one protease inhibitor.