Genetics and HIV-1 Protease Inhibitors

• Status: Completed
• Trial end date: 2008-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluated the blood levels of atazanavir according to a genetic makeup for CYP3A5 (cytochrome P450 3A5, an enzyme that metabolizes atazanavir). The hypothesis was that people with a slow-metabolizing genotype would have higher blood levels of atazanavir compared to people with the normal metabolizing genotype.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Atazanavir Sulfate; HIV Protease Inhibitors; Protease Inhibitors

Criteria

Inclusion Criteria:

• Age 18 to 55 years

• Negative HIV screening antibody test

• CYP3A5 expressor status, race, and sex fit an enrollment opening.

Exclusion Criteria:

• Pregnant or breast-feeding

• Medical history of

• hepatitis B or C,

• autoimmune disease,

• active malignancy,

• kidney disease including nephrolithiasis

• Organ dysfunction manifested by

• liver transaminases or

• serum creatinine >1.25 times the upper limit of normal, or

• any comprehensive metabolic test (except asymptomatic unconjugated hyperbilirubinemia), blood count, or lipid value > Grade I according to Division of AIDS (DAIDS) adverse drug event grading system (appendix).

• Medical history of arrhythmias (including atrial fibrillation, atrioventricular block, and/or pacemaker)

• Any QT interval abnormalities or other congenital arrhythmia syndromes on ECG or

• Any ECG abnormality that in the opinion of the investigators would preclude entry into the study.

• Medical history of any serious heart condition including:

• congestive heart failure,

• myopathies,

• coronary artery disease, or

• unexplained syncope.

• Medical history of bleeding disorders (i.e., hemophilia)

• Hyperlipidemia

• Any prescription, herbal, recreational, or over-the-counter medication contraindicated with ritonavir or atazanavir including:

• substrates/inhibitors/inducers of CYP3A/P-gp,

• cardio-active medication, or

• medications that alter the acid in the stomach. The study investigators will review each concurrent medication on a case-by-case basis.

• Inability to refrain from grapefruit or grapefruit juice during the study.

• Investigational drugs within the last 30 days.

• Active alcohol / recreational drug abuse,

• Inability to give informed consent.

• A body mass index below 18.5 or above 34.