Evaluation of Patients Who Have Not Had Success With Zidovudine

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001025
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  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 2

Study Type: Interventional
Study Design: Primary Purpose: 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
Study Completion Date: May 1995
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
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: 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
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
United States, Colorado
Kaiser Permanente Franklin Med Ctr
Denver, Colorado, United States, 80262
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Illinois
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
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
Chicago, Illinois, United States, 60611
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 / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001025     History of Changes
Other Study ID Numbers: ACTG 194, 11170
Study First Received: November 2, 1999
Last Updated: March 28, 2012
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

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

ClinicalTrials.gov processed this record on October 21, 2014