Genetics and HIV-1 Protease Inhibitors

University of Colorado Denver (CU Denver)

Status and phase

Completed

Phase 4

Conditions

HIV

Treatments

Drug: Atazanavir

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01388543

R03AI068438 (U.S. NIH Grant/Contract)

06-0428

BMSV-338 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment

31 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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.