Research Triangle Park,
The purpose of this study is to see if it is safe and effective to give the protease
inhibitor (PI) amprenavir (APV) to patients with fat production and distribution problems
associated with other PIs.
Protease inhibitors are very effective in treating HIV-1 disease. However, patients who take
these drugs often have problems, such as hyperlipidemia (an increased level of fat in the
blood) and lipodystrophy (problems with the way fat is produced and distributed in the
body). Doctors do not know exactly how PIs are related to these problems. APV has been shown
to be safe and effective in lowering plasma viral loads (level of HIV in the blood). APV may
be useful for patients who develop complications associated with other PIs.
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.
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
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.
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.
Previous treatment with APV.
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.
Prior treatment with at least one protease inhibitor.