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

Primary Purpose

HIV Infections, AIDS

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tenofovir
Hydroxyurea
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Cell Cycle Agents

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Maryland, Institute of Human Virology

Outcomes

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.
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.
These tests will be done to monitor Safety and tolerability

Full Information

First Posted
June 23, 2006
Last Updated
May 6, 2021
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT00344981
Brief Title
Safety and Durability ofTenofovir and a Cell Cycle Agent for Viral Suppression
Acronym
HADIT
Official Title
A Study to Probe The Safety And Durability of Tenofovir And a Cell Cycle Agent to Maintain Viral Suppression
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
November 2006 (Actual)
Study Completion Date
November 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, AIDS
Keywords
Cell Cycle Agents

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Tenofovir
Other Intervention Name(s)
Viread
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxyurea
Other Intervention Name(s)
Hydrea
Intervention Description
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.
Primary Outcome Measure Information:
Title
Loss of viral suppression during maintenance therapy, defined by 3 consecutive viral load measurements greater than 50c/ml over a 48- week period.
Description
Viral load measurements will be done throughout the study to monitor for viral suppression
Time Frame
At any point during the 48 week study
Secondary Outcome Measure Information:
Title
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.
Description
These tests will be done to monitor Safety and tolerability
Time Frame
Throughout the 48 week study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert R. Redfield, MD
Organizational Affiliation
University of Maryland, School of Medcine, Department of Infectious Disease
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland, Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

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Safety and Durability ofTenofovir and a Cell Cycle Agent for Viral Suppression

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