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

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:
NCT00001045
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Nevirapine
Drug: Zidovudine
Drug: Didanosine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 300
Study Completion Date: October 1998
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT00001045

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

Additional Information:
Publications:
Slade DE, Vavro CL, Stapleton JT, Swack N, StClair MH. A novel mutation at codon 215 of HIV RT. Int Conf AIDS. 1993 Jun 6-11;9(1):239 (abstract no PO-A26-0625)
Mayers D, Merigan T, Gilbert P. T215Y/F mutation associated with zidovudine (ZDV) resistance leads to poor response to ZDV+ddI or ZDV+ddI+NVP: ACTG244/RV79. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:91 (abstract no 129)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001045     History of Changes
Other Study ID Numbers: ACTG 244, 11221
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
Zidovudine
Nevirapine

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
Nevirapine
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 23, 2014