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Evaluation of Patients Who Have Not Had Success With Zidovudine
This study has been completed.
First Received: November 2, 1999   Last Updated: August 6, 2008   History of Changes
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001025
  Purpose

To determine the relationship of viral susceptibility to zidovudine (AZT) and baseline viral load (as determined by plasma viremia and quantitative endpoint dilution). To determine the relationship between viral load and susceptibility during different antiretroviral therapy strategies. To correlate measures of viral load and short term clinical and laboratory markers (such as weight, CD4 count, p24 antigenemia, and beta2 microglobulin) on the different therapy arms. High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Drug: Didanosine
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: A Study to Evaluate the Short-Term Clinical and Virologic Significance of Zidovudine Resistance

Resource links provided by NLM:


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

Estimated Enrollment: 120
Detailed Description:

High-grade resistance to AZT has been detected in HIV isolates from approximately 25 percent of individuals with AIDS who received AZT for at least 1 year. To elucidate the clinical significance of in vitro AZT resistance, it is necessary to distinguish between clinical failure caused by AZT resistance and clinical decompensation caused by other factors.

One hundred-twenty patients who have been receiving AZT for at least 1 year are randomized to 1) continue with AZT, 2) switch to treatment with didanosine at 1 of 2 doses, or 3) receive both AZT and ddI. Treatment is given for 16 weeks, with a possible extension to 32 weeks. Patients are followed at weeks 2, 4, 8, 12, and 16. For analysis purposes only, patients are stratified according to degree of susceptibility of HIV isolates to AZT.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), Mycobacterium tuberculosis, or Herpes simplex virus, or against other opportunistic infections as indicated.
  • Corticosteroids for no longer than 21 days (only as part of PCP therapy).
  • Erythropoietin and G-CSF.

Patients must have:

  • Documented HIV-seropositivity.
  • CD4 count 100 - 300 cells/mm3.
  • Prior continuous AZT dose = or > 300 mg/day for 1 year or longer.

Prior Medication: Required:

  • AZT for at least 1 year prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Medical contraindication or is considered noncompliant in the opinion of the investigator.
  • Peripheral neuropathy = or > grade 2.

Concurrent Medication:

Excluded:

  • Anti-HIV agents other than study drugs.
  • Biologic response modifiers (other than erythropoietin or G-CSF).
  • Systemic cytotoxic chemotherapy.
  • Regularly prescribed medications (such as antipyretics, analgesics, allergy medications) that are associated with an increased risk of pancreatitis, peripheral neuropathy, or bone marrow suppression.

Concurrent Treatment:

Excluded:

  • Radiation therapy.

Patients with the following prior conditions are excluded:

  • History of acute or chronic pancreatitis, gout, or uric acid nephropathy.

Prior Medication:

Excluded:

  • Other antiretrovirals besides AZT.
  • ddI or ddC for more than 30 days within the past year or any time within 3 months prior to study entry.
  • Acute therapy for an infection or other medical illness within 14 days prior to study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001025

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
Kaiser Permanente Franklin Med Ctr
Denver, Colorado, United States, 80262
United States, Illinois
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
Chicago, Illinois, United States, 60611
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Massachusetts
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Corey L
Study Chair: Cavert W
Study Chair: Coombs R
  More Information

Additional Information:
Publications:
Cavert W, Coombs RW, Kuritzkes D, Grimes J, Stein D, Rojo W, Beatty C, Winters M, Corey L. Baseline zidovudine (ZDV) susceptibility, codon 215 mutation, viral load and syncytium-inducting characteristics(SI) of HIV isolates from ACTG protocol 194. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:137
Reichelderfer PS, Coombs RW. Multifactorial analysis of the inverse relationship between viral load and CD4+ cell count. Int Conf AIDS. 1996 Jul 7-12;11(2):277 (abstract no ThB4148)

Study ID Numbers: ACTG 194
Study First Received: November 2, 1999
Last Updated: August 6, 2008
ClinicalTrials.gov Identifier: NCT00001025     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Virus Replication
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine

Study placed in the following topic categories:
Antimetabolites
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Antiviral Agents
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Didanosine
Anti-Retroviral Agents
HIV Infections
Sexually Transmitted Diseases
Retroviridae Infections

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

ClinicalTrials.gov processed this record on July 02, 2009