Comparison of Three Anti-HIV Drug Combinations in HIV-Infected Patients With No Symptoms of the Disease

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Double-Blinded, Randomized Trial Comparing Zidovudine (AZT) Versus AZT Plus Didanosine (ddI) Versus AZT Plus ddI Plus Nevirapine in Asymptomatic Patients on AZT Monotherapy Who Develop a Mutation at Codon 215 of HIV Reverse Transcriptase in Serum/Plasma Viral RNA

To validate that the alteration of codon 215 of reverse transcriptase in plasma virus precedes the increase in viral burden as measured in the peripheral blood and the decline in CD4 count that have been observed in association with clinical failure on zidovudine (AZT). To determine whether alternative regimens of antiretroviral agents alter the course of viral burden as measured in the peripheral blood and CD4 changes in patients with HIV infection. To obtain further data on the safety and immunologic and virologic response to AZT/didanosine/nevirapine.

Of the HIV-1 mutations reported to be associated with zidovudine resistance, the mutation at codon 215 of the reverse transcriptase gene is the most commonly occurring and has the greatest impact on susceptibility. When this mutation appears, a change in drugs may prevent further immunologic and virologic deterioration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Of the HIV-1 mutations reported to be associated with zidovudine resistance, the mutation at codon 215 of the reverse transcriptase gene is the most commonly occurring and has the greatest impact on susceptibility. When this mutation appears, a change in drugs may prevent further immunologic and virologic deterioration.

Initially, all patients receive AZT alone. After detection of a 215 mutation in plasma RNA, patients are randomized to one of three treatment arms: AZT alone, AZT plus ddI, or AZT/ddI plus nevirapine. Patients are followed every 8 weeks and receive treatment for up to 4 years.

AS PER AMENDMENT 5/9/96: All AZT monotherapy options have been eliminated. Patients will be randomized to either Arm II or Arm III, regardless of their codon 215 status. All patients who were randomized to Arm I following a mutation at codon 215 will be rerandomized to Arm II or Arm III. All patients who were randomized to either Arm II or Arm III following a mutation at codon 215 will remain on their initial randomized assignment.

Study Type

Interventional

Enrollment

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Bayamon, Puerto Rico, 00956
        • Ramon Ruiz Arnau Univ Hosp / Pediatrics
      • San Juan, Puerto Rico, 009367344
        • San Juan City Hosp
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Ctr
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • 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
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • District of Columbia
      • Washington, District of Columbia, United States, 200102916
        • Children's Hosp of Washington DC
      • Washington, District of Columbia, United States, 20007
        • Georgetown Univ Med Ctr
      • Washington, District of Columbia, United States, 20037
        • George Washington Univ / Hershey Med Ctr
      • Washington, District of Columbia, United States, 20307
        • Walter Reed Army Med Ctr
    • Georgia
      • Atlanta, Georgia, United States, 30306
        • Emory Univ Hosp / Pediatrics
      • Atlanta, Georgia, United States, 303652225
        • Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ of Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Queens Med Ctr
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Univ of Iowa Hosp and Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
      • Baltimore, Maryland, United States, 212052196
        • State of MD Div of Corrections / Johns Hopkins Univ Hosp
      • Bethesda, Maryland, United States, 208995000
        • Natl Naval Med Ctr
      • Rockville, Maryland, United States, 20850
        • Fitzsimmons Army Med Ctr
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med Ctr
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Med Clinic
      • Saint Paul, Minnesota, United States, 55101
        • St Paul Ramsey Med Ctr
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ of Nebraska Med Ctr
    • New York
      • Albany, New York, United States, 122083479
        • Albany Med College / Division of HIV Medicine A158
      • Albany, New York, United States, 122083479
        • Adirondack Med Ctr at Saranac Lake
      • Albany, New York, United States, 122083479
        • Mid - Hudson Care Ctr
      • Bronx, New York, United States, 10461
        • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
      • Bronx, New York, United States, 10465
        • Jack Weiler Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr Adolescent AIDS Program
      • Bronx, New York, United States, 10461
        • Montefiore Family Health Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • North Central Bronx Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Comprehensive Health Care Ctr / Bronx Municipal Hosp
      • Buffalo, New York, United States, 14215
        • SUNY / Erie County Med Ctr at Buffalo
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10037
        • Harlem Hosp Ctr
      • New York, New York, United States, 100323784
        • Columbia Presbyterian Med Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY / State Univ of New York
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Med Ctr
      • Raleigh, North Carolina, United States, 27610
        • Wake County Dept of Health
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth Med Ctr
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
      • Toledo, Ohio, United States, 43699
        • Med College of Ohio
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 170330850
        • Milton S Hershey Med Ctr
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Philadelphia, Pennsylvania, United States, 191075098
        • Thomas Jefferson Univ Hosp
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt Univ Med Ctr
    • Texas
      • Galveston, Texas, United States, 775550435
        • Univ of Texas Galveston
      • Lackland Air Force Base, Texas, United States, 782365300
        • Wilford Hall Med Ctr
      • San Antonio, Texas, United States, 78284
        • Brooke Army Med Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia.
  • Antibiotics, antifungals, and antiviral medications, as clinically indicated.
  • Regularly prescribed medication such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, or any other medications deemed appropriate by the primary care provider.

Concurrent Treatment:

Allowed:

  • Limited localized radiation therapy to the skin.

Prior Medication: Required:

  • AZT (minimum 300 mg/day) for at least 1 month (uninterrupted) but no more than 2 years immediately prior to study entry.

Patients must have:

  • Asymptomatic HIV infection.
  • CD4 count 300-600 cells/mm3.
  • No plasma/serum PCR for codon 215 mutation at screening.
  • Prior AZT monotherapy.

NOTE:

  • All Department of Defense (DOD)-eligible patients must be at least 18 years of age. Enrollment of women is encouraged.

AS PER AMENDMENT 04/03/95:

  • DOD female patients must have a negative pregnancy test within 48 hours prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Symptomatic grade 2 or worse peripheral neuropathy.
  • Unable to swallow capsules and tablets.
  • Other medical condition that contraindicates study participation.

Concurrent Medication:

Excluded:

  • Systemic cytotoxic chemotherapy.
  • Biologic response modifiers (such as interferon, ampligen, or PEG-IL2).
  • Anti-HIV agents other than study drugs.
  • Other investigational agents.
  • Foscarnet unless clinically indicated for unresponsive herpes virus infection.
  • Chronic antacid or H-2 blocker use.
  • Rifampin or rifamycin class agents.
  • Antibiotics containing clavulanic acid.

Concurrent Treatment:

Excluded:

  • Radiation therapy other than limited localized therapy to skin.

Patients with the following prior condition are excluded:

  • History of pancreatitis.

Prior Medication:

Excluded:

  • Prior therapy with nucleoside or non-nucleoside antiretroviral agents other than AZT.
  • Immune modulating therapies (e.g., IFN-alpha, gp160) within 60 days prior to screening.

Prior Treatment:

Excluded:

  • Blood transfusion within the preceding 2 weeks.

Illicit drug or alcohol abuse.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb
Glaxo Wellcome

Investigators

  • Study Chair: Mayers DL

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

October 1, 1998

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 4, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 244
  • 11221 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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