Salvage Treatment, Resistance Testing, and Withdrawal of Anti-HIV Drugs for HIV Patients Failing Current Anti-HIV Treatment

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00011128
First received: February 10, 2001
Last updated: August 6, 2008
Last verified: May 2004
  Purpose

The purpose of this study is to test another way to control the amount of HIV in the blood (viral load).

Studies show that stopping all anti-HIV drugs for a time before switching to new anti-HIV drugs may improve the response in some individuals who are failing treatment. Other studies suggest a benefit if drug-resistance tests are used in selecting a new anti-HIV drug treatment. This study tests the effect of stopping anti-HIV drugs for a time before switching to anti-HIV drugs selected using drug-resistance test results.


Condition Intervention Phase
HIV Infections
Behavioral: Antiretroviral Treatment Interruption
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Evaluation of the Role of Temporary Cessation of Antiretroviral Treatment and Resistance Testing-Based Selection of Antiretroviral Drugs in the Virologic Response to Salvage Therapy for Heavily Treatment-Experienced HIV-Infected Individuals Failing Current Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 140
Detailed Description:

Virologic failure occurs in a large proportion of individuals receiving treatment with combination antiretroviral therapy. Studies suggest that treatment interruption prior to initiation of a multiple-drug rescue regimen may improve virologic response in individuals who have failed several prior antiretroviral regimens. Other studies suggest there is a virologic benefit derived from using genotypic or phenotypic resistance testing in selecting salvage therapy regimens for patients failing antiretroviral therapy. This study tests the hypothesis that salvage regimens selected on the basis of HIV-1 resistance genotype, phenotype [AS PER AMENDMENT 02/19/02: virtual phenotype], and treatment history will be more effective if there is a period of treatment interruption before initiating that regimen.

Patients continue their antiretroviral therapy until randomization. Based on the results of the pre-entry genotype and phenotype [AS PER AMENDMENT 02/19/02: virtual phenotype] tests and treatment history, an individualized salvage therapy regimen (not provided by the study) is selected by the site investigator(s). Additionally, patients start or continue maintenance therapy (not provided by the study) for opportunistic infections (OIs). Patients are randomized to 1 of 2 treatment arms. In Arm A, patients have antiretroviral treatment interruption for a period of 16 weeks (Step 1), followed by initiation of the [AS PER AMENDMENT 02/19/02: best available] salvage therapy regimen (Step 2). [AS PER AMENDMENT 02/19/02: Patients in Arm A will be placed immediately on their individualized salvage regimen before the end of the 16-week period of treatment interruption if their CD4 count falls below a defined threshold, or if they develop a new OI]. In Arm B, patients switch immediately to the salvage therapy regimen. [AS PER AMENDMENT 02/15/01: Patients who become pregnant during Step 1 of Arm A must be advised to begin their selected, individualized salvage therapy regimen or a modified salvage regimen. Patients who become pregnant during Step 2 of Arm A or Arm B have therapy evaluated and undergo any changes required by their pregnancy.] Patients in both arms are monitored for plasma HIV-1 RNA levels, CD4+ and CD8+ cell counts, and HIV drug resistance genotypes and phenotypes for a duration of 64 weeks from randomization. Patients in Arm A are also monitored for immune reactivation by measurement of T-cell subsets and plasma cytokines during treatment interruption. Patients may participate in a virology substudy (A5100s) and an immunology substudy (A5104s). [AS PER AMENDMENT 02/19/02: Patients who volunteer to participate in the substudies must be registered to the main study at the same time they are registered to a substudy.]

  Eligibility

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

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-infected.
  • Are likely to have drug-resistant HIV from having taken all types of anti-HIV drugs (protease inhibitors [PIs], nucleoside reverse transcriptase inhibitors [NRTIs], and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), and having failed treatment prior to the current treatment for reasons other than toxicity.
  • Are currently receiving anti-HIV treatment with at least 3 drugs. Low doses of ritonavir (100 to 200 mg twice daily) taken with 1 other PI is counted as a single PI.
  • Are currently failing treatment due to a high viral load (amount of HIV in the blood).
  • Have had a new anti-HIV drug combination selected.
  • Are at least 18 years old.
  • This study has been changed to remove CD4 counts as an inclusion criterion. In the previous version of the protocol, patients were required to have a CD4 count of 150 cells/ml or more within 42 days prior to study entry.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have stopped treatment for more than 4 weeks in the past 6 months.
  • Are pregnant or breast-feeding.
  • Have cancer that requires systemic treatment or radiation.
  • Have received the following medications affecting the immune system within 14 days before entry: erythropoietin; Granulocyte Colony Stimulating Factor (G-CSF), including Granulocyte Macrophage Colony Stimulating Factors (GM-CSF); interleukins; or therapeutic HIV vaccines.
  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: NCT00011128

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Willow Clinic
Menlo Park, California, United States, 94025
Univ of California, San Diego
San Diego, California, United States, 92103
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Hawaii
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
The CORE Ctr
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
Wishard Hosp
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, New York
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Cornell Univ Med Ctr
New York, New York, United States, 10021
Cornell Clinical Trials Unit - Chelsea Clinic
New York, New York, United States, 10011
Beth Israel Med Ctr
New York, New York, United States, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Community Health Network Inc
Rochester, New York, United States, 14642
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Univ of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 37203
United States, Texas
Children's Med Ctr of Dallas
Dallas, Texas, United States, 75235
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Constance A Benson, MD University of Colorado, Denver
Study Chair: John Mellors, MD University of Pittsburgh
Study Chair: Diane Havlir, MD University of California, San Francisco
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00011128     History of Changes
Other Study ID Numbers: ACTG A5086, AACTG A5086, Substudy AACTG A5100s, Substudy AACTG A5104s
Study First Received: February 10, 2001
Last Updated: August 6, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Resistance, Microbial
Microbial Sensitivity Tests
Salvage Therapy
Anti-HIV Agents
Viral Load
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

ClinicalTrials.gov processed this record on September 18, 2014