Safety and Durability ofTenofovir and a Cell Cycle Agent for Viral Suppression (HADIT)

This study has been completed.
Sponsor:
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT00344981
First received: June 23, 2006
Last updated: May 21, 2010
Last verified: May 2010
  Purpose

Study Hypothesis Evaluation of the durability of the combination Tenofovir and Hydroxyurea to maintain viral suppression below 50 copies/ml in volunteers who have achieved viral suppression on a standard HAART regimen.


Condition Intervention
HIV Infections
AIDS
Drug: Tenofovir
Drug: Hydroxyurea

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Probe The Safety And Durability of Tenofovir And a Cell Cycle Agent to Maintain Viral Suppression

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Loss of viral suppression during maintenance therapy, defined by 3 consecutive viral load measurements greater than 50c/ml over a 48- week period. [ Time Frame: At any point during the 48 week study ] [ Designated as safety issue: Yes ]
    Viral load measurements will be done throughout the study to monitor for viral suppression


Secondary Outcome Measures:
  • Laboratory Abnormalities: Routine measurements of hematology, serum chemistry, CD4 cell count, lipid profiles, and HIV-1 viral load will be performed. Viral genotypes will be performed with failure to maintain viral suppression. [ Time Frame: Throughout the 48 week study ] [ Designated as safety issue: Yes ]
    These tests will be done to monitor Safety and tolerability


Enrollment: 9
Study Start Date: June 2003
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tenofovir
    Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir.
    Other Name: Viread
    Drug: Hydroxyurea
    Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir. Volunteers will continue on this regimen for 48 weeks. Patients will be monitored for immunological and virological parameters as well as the incidence of toxicity and side effects during the study. If a patient's viral load reaches >400 copies/ml on 3 consecutive measurements over a 6 week period, they will be terminated from the study and started back on their HAART.
    Other Name: Hydrea
Detailed Description:

This is a 48 week open-label, randomized study comparing the safety and durability of a highly active de-intensified therapy (Tenofovir/Hydroxyurea) to a simplified standard of care therapy (Tenofovir plus 3TC or Emtriva plus Sustiva or Nevirapine) to maintain a durable viral suppression.

Up to 20 subjects with chronic HIV-1 infection, suppressed on highly active antiretroviral therapy, and without evidence of viral resistance will be enrolled in this study. Their present HAART therapy will be stopped.

Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir. The other half will be randomized to Sustiva 600 mg qd or Nevirapine 200 mg twice a day); Tenofovir 300 mg qd, 3TC 300 mg qd or Emtriva 200 mg once a day. Volunteers will continue on this regimen for 48 weeks. Patients will be monitored for immunological and virological parameters as well as the incidence of toxicity and side effects during the study. If a patient's viral load reaches >400 copies/ml on 3 consecutive measurements over a 6 week period, they will be terminated from the study and started back on their HAART.

  Eligibility

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

Inclusion Criteria:

  1. Diagnosis of HIV infection based on western blot testing, ELISA, or HIV viral load
  2. Age greater than or equal to 18 years
  3. CD4 count greater than or equal to 200c/ml.
  4. On a standard HAART regimen of 2 or 3 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor or 3 nucleoside reverse transcriptase inhibitors (2-3NRTI's + PI or 2-3NRTI's +NNRTI or 3NRTI's).
  5. On stable, continuous HAART regimen for greater than or equal to 3 months,
  6. Viral load less than or equal to 400c/ml on all measurements in the preceding 6 months with at least 2 measurements (screening viral load can be included if needed)
  7. Viral load less than or equal to 50c/ml at screening
  8. Subject able to comply with the study protocol
  9. Signed informed consent
  10. No history of antiretroviral failure that is suspected to be from or resulted in antiretroviral resistance.

Exclusion Criteria:

  1. Serious HIV related or non HIV related carcinoma requiring chemotherapy
  2. Recent serious opportunistic infection, such as progressive multifocal leukoencephalopathy, CMV disease, cryptococcus meningitis, cerebral toxoplasmosis, but not excluding other infections in which successful treatment may be judged to be placed at risk if antiretroviral therapy was de intensified.
  3. Known or suspected intolerance or hypersensitivity to Hydroxyurea
  4. Grade 3 or higher neutropenia (using ACTG grading table)
  5. Grade 2 or higher thrombocytopenia (using ACTG grading table)
  6. Grade 2 or higher LFT abnormalities (using ACTG grading table)
  7. History of pancreatitis, or risk factors associated with pancreatitis (more then two drinks containing alcohol/day, triglyceride levels greater than 400, and pancreatic enzymes greater then 1.5x normal)
  8. Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
  9. Chronic diarrhea
  10. Pregnancy or breastfeeding
  11. Unwillingness to use effective barrier contraception or abstinence
  12. The use of systemic corticosteroids, or other systemic immunosuppressive medications; the use of cholestyramine; the use of probenecid or other inhibitors of renal tubular secretion
  13. Genotypic or phenotypic testing documenting major resistance to any antiretroviral agents
  14. Active substance or mental health concerns that are judged to place a significant limitation on medication adherence.
  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: NCT00344981

Locations
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Robert R. Redfield, MD University of Maryland, School of Medcine, Department of Infectious Disease
  More Information

No publications provided

Responsible Party: Dr. Robert R. Redfield, Institute of Human Virology
ClinicalTrials.gov Identifier: NCT00344981     History of Changes
Other Study ID Numbers: H-22407
Study First Received: June 23, 2006
Last Updated: May 21, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Cell Cycle Agents

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
Tenofovir disoproxil
Hydroxyurea
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
Antineoplastic Agents
Antisickling Agents
Hematologic Agents

ClinicalTrials.gov processed this record on September 22, 2014