Artery Elasticity After Switch From Epzicom to Truvada

Recent research as suggested that use of the HIV medication abacavir (Ziagen, or co-formulated with lamivudine as Epzicom) may increase risk for heart disease, though findings from multiple studies have been inconsistent. This pilot study will examine vascular function, a marker of heart disease risk, among patients taking abacavir as part of their HIV medications and are then randomized to: 1) switch to tenofovir, another HIV medication, or 2) continue to take abacavir.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Tenofovir disoproxil

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States
      • Abbott Northwestern Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (≥18 years) males or non-pregnant females, non-lactating females.
• HIV-infected participants currently receiving fixed-dose abacavir/lamivudine based regimen for ≥3 months preceding the screening visit.
• HIV-infection documented by a positive HIV-1 antibody (confirmatory western-blot) or an HIV RNA level ≥1000 copies/mL
• Two consecutive plasma HIV RNA concentrations below the limit of detection for clinical-based assays used for HCMC and ANW HIV clinics. The 1st HIV RNA concentration must be at least 3 months prior to study entry.
• Subjects receiving lipid lowering agents will be allowed; however, dosing for these medications must be stable for ≥3 months prior to study entry

• Adequate renal function defined as a calculated creatinine clearance (CLCr) ≥50 mL/min according to the Cockcroft-Gault formula:

  • MALE: (140 - age in years) x (wt in kg) = CLCr (mL/min) 72 x (serum creatinine in mg/dL)
  • FEMALE: (140 - age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 72 x (serum creatinine in mg/dL)
• Negative serum pregnancy test (females of childbearing potential only)
• Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN).
• Males and females (of childbearing potential) must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug (refer to Appendix A for definitions of 'childbearing potential' and 'highly effective method of birth control')

Exclusion Criteria:

• Subjects with known resistance to abacavir, lamivudine, tenofovir DF, or emtricitabine at anytime in the past (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations).
• A new AIDS-defining condition diagnosed (with the exception of CD4 criteria) within 30 days of baseline
• Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic or cytotoxic potential within 3 months of study entry or the expectation for such therapy at the time of enrollment
• Proven or suspected acute hepatitis in the 30 days prior to study entry

• Receiving ongoing therapy with any of the following (administration of any of the following medications must be discontinued at least 30 days prior to the baseline visit and for the duration of the study period):

  • Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, other agents with significant nephrotoxic potential)
  • Adefovir dipivoxil
  • Probenecid
  • Systemic chemotherapeutic agents (i.e., cancer treatment medications)
  • Systemic corticosteroids
  • Interleukin-2 (IL-2)
• Evidence of gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with subject adherence
• Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Participants with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and are not anticipated to require systemic therapy during the study.
• Active, serious infections (other than HIV-1 infection) requiring parenteral antimicrobial therapy within 15 days prior to screening.
• Prior history of significant renal or bone disease.
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
• Known hypersensitivity to the study drugs, the metabolites or formulation excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Abacavir; Participants randomized to this arm will continue abacavir and their other HIV medications with no changes	Drug: Tenofovir disoproxil; Participants taking an abacavir-based HIV treatment regimen will be randomized to switch to a tenofovir-based regimen or continue taking abacavir.
Experimental: Tenofovir; Participants randomized to this arm will switch from taking abacavir (co-formulated with lamivudine as Epzicom) and start taking tenofovir (co-formulated with emtricitabine as Truvada), and continue their other HIV medications	Drug: Tenofovir disoproxil; Participants taking an abacavir-based HIV treatment regimen will be randomized to switch to a tenofovir-based regimen or continue taking abacavir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Small Artery Elasticity (mL/mmHg x100) From Baseline to Week 24	Small artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the small (and large) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease that predicts risk for future cardiovascular events.	Change from baseline to 24 weeks
Outcome Was Change in Large Artery Elasticity (mL/mmHg x100) From Baseline to Week 24	Large artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the large (and small) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease.	Change from baseline to 24 weeks

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute
• Investigators: Principal Investigator: Jason Baker, MD, MS, University of Minnesota; HCMC

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 19, 2009
• First Submitted That Met QC Criteria: October 19, 2009
• First Posted (Estimate): October 20, 2009

Study Record Updates

• Last Update Posted (Estimate): October 8, 2012
• Last Update Submitted That Met QC Criteria: October 3, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; HIV Infection; Treatment experienced; Abacavir; Artery Elasticity
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: PCC-004