Evaluation of Patients Who Have Not Had Success With Zidovudine

A Study to Evaluate the Short-Term Clinical and Virologic Significance of Zidovudine Resistance

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Didanosine

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.

• Study Type: Interventional
• Enrollment: 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama at Birmingham
  • California
    • San Francisco, California, United States, 941102859
      • San Francisco Gen Hosp
    • San Jose, California, United States, 951282699
      • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
    • Stanford, California, United States, 943055107
      • San Mateo AIDS Program / Stanford Univ
  • Colorado
    • Denver, Colorado, United States, 80262
      • Univ of Colorado Health Sciences Ctr
    • Denver, Colorado, United States, 80262
      • Kaiser Permanente Franklin Med Ctr
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ Med School
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 60611
      • Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Med Ctr of Springfield
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Univ of Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 681985130
      • Univ of Nebraska Med Ctr
  • New York
    • Brooklyn, New York, United States, 112032098
      • SUNY / Health Sciences Ctr at Brooklyn
    • Buffalo, New York, United States, 14215
      • SUNY / Erie County Med Ctr at Buffalo
    • Rochester, New York, United States, 14642
      • Univ of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY / State Univ of New York
  • Washington
    • Seattle, Washington, United States, 981224304
      • Univ of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Bristol-Myers Squibb; Glaxo Wellcome
• Investigators: Study Chair: Coombs R; Study Chair: Cavert W

Publications and helpful links

General 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 record dates

Study Major Dates

• Study Completion (Actual): May 1, 1995

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Didanosine; Zidovudine; Virus Replication
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Didanosine
• Other Study ID Numbers: ACTG 194; 11170 (Registry Identifier: DAIDS ES Registry Number)