Effect of Atazanavir on Endothelial Function in HIV-Infected Patients

NCT00447070 | Completed Phase 4

• 1 other identifier: ICN 99034
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections; Dyslipidemia

Keywords

HIV-infection; Dyslipidemia; Endothelial Dysfunction; Atherosclerosis; Protease inhibitor; treatment experienced

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Changes in plasma lipid profiles and further clinical chemistry parameters after 6 months of treatment compared to baseline.

Interventions

ATAZANAVIR DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Foundation for Cardiovascular Research, Zurich: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University Hospital Zurich, Infectiology

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (1)

• Flammer AJ, Vo NT, Ledergerber B, Hermann F, Gamperli A, Huttner A, Evison J, Baumgartner I, Cavassini M, Hayoz D, Quitzau K, Hersberger M, Sudano I, Ruschitzka F, Luscher TF, Noll G, Weber R. Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: randomised controlled trial. Heart. 2009 Mar;95(5):385-90. doi: 10.1136/hrt.2007.137646. Epub 2008 Jul 24.

  PMID: 18653575 RESULT

MeSH Terms

Conditions

HIV Infections; Dyslipidemias; Acquired Immunodeficiency Syndrome; Atherosclerosis

Interventions

Atazanavir Sulfate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Slow Virus Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Rainer Weber, Prof.

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 12, 2007
• First Posted: March 14, 2007
• Study Start: August 1, 2004
• Study Completion: May 1, 2006
• Last Updated: May 27, 2009

Record last verified: 2007-03

Locations

CH (1)