Genetics and HIV-1 Protease Inhibitors

Phase 4

Completed

• Conditions: HIV
• Interventions: Drug: Atazanavir

• Registration Number: NCT01388543
• Lead Sponsor: University of Colorado, Denver

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-09
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Study First Submitted: 2011-06-28
• Study First Submitted QC: 2011-07-01
• Study First Posted: 2011-07-06
• Status Verified: 2019-10
• Results First Submitted: 2019-10-11
• Results First Submitted QC: 2019-10-31
• Last Update Submitted: 2019-10-31
• Results First Posted: 2019-11-19
• Last Update Posted: 2019-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Age 18 to 55 years
• Negative HIV screening antibody test
• CYP3A5 expressor status, race, and sex fit an enrollment opening.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CYP3A5 Expressors	Atazanavir	A pre-screening genetic test determines CYP3A5 expressor status
CYP3A5 Non-expressors	Atazanavir	A pre-screening genetic test determines CYP3A5 non-expressor status

Primary Outcome Measures

Name	Time	Method
Day 7 Atazanavir Oral Clearance	Day 7	Measure atazanavir oral clearance in genetically-determined CYP3A5 expressors versus CYP3A5 non-expressors

Trial Locations

Locations (1)

University of Colorado Denver and Health Sciences Center; 🇺🇸 Aurora, Colorado, United States