Genetics and HIV-1 Protease Inhibitors
Condition: HIV
Intervention: Atazanavir
Intervention description: Atazanavir 400mg once daily for 7 days followed by atazanavir 300mg plus ritonavir 100mg for 7 days
Intervention MeSH terms: Atazanavir Sulfate
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetics; Clinical Pharmacology; Pharmacogenomics; HIV

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.
    

Eligibility 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.