A Study to Probe the Safety and Durability of Tenofovir and a Cell Cycle Agent to Maintain Viral Suppression - Full Text View

Sponsored by:	University of Maryland
Information provided by:	University of Maryland
ClinicalTrials.gov Identifier:	NCT00344981

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

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Hydroxyurea

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

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.
Secondary Endpoints:

Secondary Outcome Measures:

1. Safety and Tolerability
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.

Estimated Enrollment:	20
Study Start Date:	June 2003
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

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:

Diagnosis of HIV infection based on western blot testing, ELISA, or HIV viral load
Age greater than or equal to 18 years
CD4 count greater than or equal to 200c/ml.
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).
On stable, continuous HAART regimen for greater than or equal to 3 months,
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)
Viral load less than or equal to 50c/ml at screening
Subject able to comply with the study protocol
Signed informed consent
No history of antiretroviral failure that is suspected to be from or resulted in antiretroviral resistance.

Exclusion Criteria:

Serious HIV related or non HIV related carcinoma requiring chemotherapy
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.
Known or suspected intolerance or hypersensitivity to Hydroxyurea
Grade 3 or higher neutropenia (using ACTG grading table)
Grade 2 or higher thrombocytopenia (using ACTG grading table)
Grade 2 or higher LFT abnormalities (using ACTG grading table)
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)
Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
Chronic diarrhea
Pregnancy or breastfeeding
Unwillingness to use effective barrier contraception or abstinence
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
Genotypic or phenotypic testing documenting major resistance to any antiretroviral agents
Active substance or mental health concerns that are judged to place a significant limitation on medication adherence.

Contacts and Locations

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

Study ID Numbers:	H-22407
Study First Received:	June 23, 2006
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00344981 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Maryland:

Cell Cycle Agents

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Hydroxyurea
Acquired Immunodeficiency Syndrome
Benzocaine
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors

Virus Diseases
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Hydroxyurea
Antineoplastic Agents
Hematologic Agents
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

RNA Virus Infections
Anti-HIV Agents
Antisickling Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on May 07, 2009