Evolution of L74V or K65R Mutations in VIremic Subjects on Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) (EVITA)

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Orlando Immunology Center
ClinicalTrials.gov Identifier:
NCT00312169
First received: April 5, 2006
Last updated: May 20, 2008
Last verified: May 2008
  Purpose

This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Subjects will be followed until a substantial loss of virologic or immunologic control requires a treatment switch. Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.

Subjects will have a screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized.

Twenty subjects (a maximum of 10 per arm) will be enrolled at 10-20 United States (U.S.) sites. If fewer than 20 subjects can be enrolled, the study may be discontinued early by the sponsor. Equal numbers of subjects on Arm A versus Arm B will be a goal.


Condition Phase
HIV Infections
Phase 4

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Evolution of L74V or K65R Mutations in VIremic Subjects on TDF or ABC (EVITA)

Resource links provided by NLM:


Further study details as provided by Orlando Immunology Center:

Estimated Enrollment: 20
Study Start Date: April 2006
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed first-time incomplete virologic suppression during treatment with at least 12 weeks of an ARV regimen consisting of TDF or ABC + FTC or 3TC + NNRTI or PI (TDF as Truvada or individually with FTC, and ABC as Epzicom or individually with 3TC). Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
  2. Screening HIV-1 RNA < 20,000 copies/mL obtained within 30 days prior to study entry.
  3. Screening CD4 cell count ≥ 200 cells/mL.
  4. Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation.
  5. Routine labs as demonstrated by last available lab panel to be:

    • Hemoglobin > 8.0 g/dL;
    • Platelet count > 50,000/mm3;
    • AST (SGOT) < 210 U/L;
    • ALT (SGPT) < 240 U/L;
    • Alkaline phosphatase < 625 U/L;
    • Total bilirubin < 3.25 mg/dL; and
    • Calculated creatinine clearance ≥ 50 as estimated by the Cockcroft-Gault equation.
  6. If participating in sexual activity that could lead to pregnancy, female study subjects must use two forms of contraception, one of which must be a barrier method.
  7. Men and women aged ≥ 18 years.
  8. Ability and willingness of subjects to give written informed consent.

Exclusion Criteria:

  1. Subjects with screening HIV-1 genotype that is wild-type or contains the resistance mutations K65R/x or L74V/x.
  2. Prior or current treatment with ARV regimen consisting of only NRTIs, ZDV or d4T, more than 2 NRTIs, ritonavir-boosted or dual PI regimen.
  3. Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. For non-serious illnesses, treatment of less than 21 days with larger doses of corticosteroids is permitted.
  4. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  5. Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restrictions.
  6. Unable to discontinue contraindicated current medications.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312169

Locations
United States, California
Special Services Adult HIV Clinic
Fresno, California, United States, 93702
AltaMed Health Services Corporation
Los Angelos, California, United States, 90022
Tarzana Treatment Center
Tarzana, California, United States, 91356
Shared Medical Research Foundation
Tarzana, California, United States, 91356
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Illinois
Northstar Medical Center
Chicago, Illinois, United States, 60657
United States, Michigan
Paul Benson, DO, PC
Berkley, Michigan, United States, 48072
United States, New York
Ricky Hsu, MD
New York, New York, United States, 10011
United States, Pennsylvania
Temple University School of Medicine, Section of Infectious Diseases
Philadelphia, Pennsylvania, United States, 19140
United States, South Carolina
Greenville Hospital System Infectious Disease Associates
Greenville, South Carolina, United States, 29605
United States, Texas
Nicholas C. Bellos, MD PA and Associates
Dallas, Texas, United States, 75204
Sponsors and Collaborators
Orlando Immunology Center
GlaxoSmithKline
Investigators
Study Director: Edwin DeJesus, MD, FACP OIC
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00312169     History of Changes
Other Study ID Numbers: COL105034 (EVITA), EVITA
Study First Received: April 5, 2006
Last Updated: May 20, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Orlando Immunology Center:
HIV
NNRTI
Incomplete virologic suppression
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir disoproxil
Tenofovir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 30, 2014