Effect of Atazanavir on Endothelial Function in HIV-Infected Patients
Condition: HIV Infections; Dyslipidemia
MeSH terms: HIV Infections; Dyslipidemias
Study type: Interventional
Phase: Phase 4

Summary: 
      It is known that certain antiviral therapies, the socalled protease inhibitors, used in the
      treatment of HIV infection has an untowarded effect on the blood vessels, promoting early
      occurence of atherosclerosis. A a newer protease inhibitor, atazanavir, has been shown to
      have no negative effect on the levels of blood cholesterol and it is hypothesized that this
      may indicate that atazanavir is less prone to induce atherosclerosis. An early sign of
      atherosclerosis is a reduced vasomotion and this study investigate the influence of
      atazanavir on functionality of the conduit blood vessels compared to that of "standard"
      antiviral therapy.
    

Detailed description: 
      Indication: Dyslipidemia Type II in HIV-Infected Patients

      Primary Objectives: Change of flow-mediated dilation in the forearm after 6 months using the
      protease inhibitor atazanavir in a potent antiviral therapy combination compared with a
      combination including current proteinase inhibitor.

      Secondary Objectives: Changes in plasma lipid profiles and further clinical chemistry
      parameters after 6 months of treatment compared to baseline.

      Study Design: This is a multicenter, observer-blind (measurements of vessel parameters and
      statistical evaluation), treatment-controlled, randomized, study with 2 treatment groups.

      Planned Total Sample Size: (40-50) eligible randomized patients (20-25 per group) from 2-5
      centers.

      Subject Selection Criteria:

        -  Men and women, 18 to 65 years old.

        -  HIV-infection, documented by HIV-antibody ELISA and either positive immunoblot for
           HIV-antibodies or presence of HIV1 in blood.

        -  Two consecutive Roche Ultrasensitive Amplicor tests showing plasma HIV-1 RNA < 50
           copies/ml within 60 days prior to study entry.

        -  CD4 count of > 100 cells/ml during 60 days prior to study entry.

        -  Stable antiretroviral therapy for at least 12 weeks prior to study entry (a protease
           inhibitor plus 2 NRTIs).

        -  Patient's treatment history allows, in the opinion of the investigator, atazanavir as
           replacement for current PI, i.e. continued viral suppression is expected based upon
           patient's treatment history and results of previous resistance testing, if available.

        -  Fasting LDL-cholesterol > 3.0 mmol/l.

      Contraindications for participation:

        -  Known coronary artery disease, hypertension, peripheral artery disease, or
           cerebrovascular disease.

        -  Diabetes mellitus.

        -  Serious illness requiring systemic treatment and/or hospitalization within 14 days prior
           to study entry.

        -  Any contraindication for study medication.

        -  Currently on non-nucleoside reverse transcriptase inhibitors (NNRTI) (previous exposure
           allowed).

        -  Previous virologic failure on proteinase inhibitor-containing regimens which was not the
           consequence of poor adherence to therapy or drug adverse events; i.e. virologic failure
           was probably due to lack of potency of drug regimen, and may consecutively have resulted
           in protease resistance mutations.

        -  Previously documented protease resistance mutations which are known to result in
           cross-resistance against atazanavir.

        -  Any lipid lowering drugs within 4 weeks prior to study entry.

        -  Testosterone or anabolic steroids unless stable therapy at least 12 weeks prior to study
           entry.

        -  Systemic glucocorticoids, long-acting inhaled steroids or other immunomodulators within
           30 days prior to study entry (prednisone < 10mg/day or equivalent is permitted.

        -  Drug or alcohol abuse, in the opinion of the investigator rendering the patient
           unreliable for participation.

        -  Participation in any other drug/treatment study.

      Test Drugs:

        1. Atazanavir capsules in daily standard dose (2 x 200 mg once daily) or

        2. Continuation of current protease inhibitor
    

Intervention name(s): ATAZANAVIR
Intervention type(s): Drug
Intervention MeSH terms: Atazanavir Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single
Primary purpose: Treatment
Keywords: HIV-infection; Dyslipidemia; Endothelial Dysfunction; Atherosclerosis; Protease inhibitor; treatment experienced