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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nevirapine
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Didanosine, Drug Therapy, Combination, Zidovudine, Nevirapine

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA CARE Ctr
  • Stanford at Kaiser / Kaiser Permanente Med Ctr
  • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
  • San Mateo AIDS Program / Stanford Univ
  • Stanford Univ Med Ctr
  • Harbor UCLA Med Ctr
  • Univ of Colorado Health Sciences Ctr
  • Georgetown Univ Med Ctr
  • Children's Hosp of Washington DC
  • George Washington Univ / Hershey Med Ctr
  • Walter Reed Army Med Ctr
  • Emory Univ Hosp / Pediatrics
  • Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
  • Queens Med Ctr
  • Univ of Hawaii
  • Indiana Univ Hosp
  • Univ of Iowa Hosp and Clinic
  • State of MD Div of Corrections / Johns Hopkins Univ Hosp
  • Johns Hopkins Hosp
  • Natl Naval Med Ctr
  • Fitzsimmons Army Med Ctr
  • Beth Israel Deaconess Med Ctr
  • Hennepin County Med Clinic
  • Univ of Minnesota
  • St Paul Ramsey Med Ctr
  • Univ of Nebraska Med Ctr
  • Adirondack Med Ctr at Saranac Lake
  • Albany Med College / Division of HIV Medicine A158
  • Mid - Hudson Care Ctr
  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
  • Comprehensive Health Care Ctr / Bronx Municipal Hosp
  • Montefiore Family Health Ctr / Bronx Municipal Hosp
  • Jack Weiler Hosp / Bronx Municipal Hosp
  • Montefiore Med Ctr / Bronx Municipal Hosp
  • Montefiore Med Ctr Adolescent AIDS Program
  • North Central Bronx Hosp / Bronx Municipal Hosp
  • SUNY / Erie County Med Ctr at Buffalo
  • Bellevue Hosp / New York Univ Med Ctr
  • Columbia Presbyterian Med Ctr
  • Harlem Hosp Ctr
  • Univ of Rochester Medical Center
  • SUNY / State Univ of New York
  • Univ of North Carolina
  • Carolinas Med Ctr
  • Wake County Dept of Health
  • Case Western Reserve Univ
  • MetroHealth Med Ctr
  • Ohio State Univ Hosp Clinic
  • Med College of Ohio
  • Milton S Hershey Med Ctr
  • Univ of Pennsylvania at Philadelphia
  • Thomas Jefferson Univ Hosp
  • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
  • Vanderbilt Univ Med Ctr
  • Univ of Texas Galveston
  • Wilford Hall Med Ctr
  • Brooke Army Med Ctr
  • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • San Juan City Hosp

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00001045
Brief Title
Comparison of Three Anti-HIV Drug Combinations in HIV-Infected Patients With No Symptoms of the Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Didanosine, Drug Therapy, Combination, Zidovudine, Nevirapine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
300 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Nevirapine
Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merigan TC
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mayers DL
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford at Kaiser / Kaiser Permanente Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
City
San Jose
State/Province
California
ZIP/Postal Code
951282699
Country
United States
Facility Name
San Mateo AIDS Program / Stanford Univ
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
Stanford Univ Med Ctr
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
Harbor UCLA Med Ctr
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Univ of Colorado Health Sciences Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Georgetown Univ Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Children's Hosp of Washington DC
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
200102916
Country
United States
Facility Name
George Washington Univ / Hershey Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Walter Reed Army Med Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20307
Country
United States
Facility Name
Emory Univ Hosp / Pediatrics
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30306
Country
United States
Facility Name
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
303652225
Country
United States
Facility Name
Queens Med Ctr
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Univ of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Univ of Iowa Hosp and Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
State of MD Div of Corrections / Johns Hopkins Univ Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
212052196
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Natl Naval Med Ctr
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
208995000
Country
United States
Facility Name
Fitzsimmons Army Med Ctr
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Beth Israel Deaconess Med Ctr
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hennepin County Med Clinic
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St Paul Ramsey Med Ctr
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Univ of Nebraska Med Ctr
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
681985130
Country
United States
Facility Name
Adirondack Med Ctr at Saranac Lake
City
Albany
State/Province
New York
ZIP/Postal Code
122083479
Country
United States
Facility Name
Albany Med College / Division of HIV Medicine A158
City
Albany
State/Province
New York
ZIP/Postal Code
122083479
Country
United States
Facility Name
Mid - Hudson Care Ctr
City
Albany
State/Province
New York
ZIP/Postal Code
122083479
Country
United States
Facility Name
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Comprehensive Health Care Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Family Health Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Jack Weiler Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10465
Country
United States
Facility Name
Montefiore Med Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Montefiore Med Ctr Adolescent AIDS Program
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
North Central Bronx Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia Presbyterian Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
100323784
Country
United States
Facility Name
Harlem Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY / State Univ of New York
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Carolinas Med Ctr
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Wake County Dept of Health
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Facility Name
Case Western Reserve Univ
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth Med Ctr
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
441091998
Country
United States
Facility Name
Ohio State Univ Hosp Clinic
City
Columbus
State/Province
Ohio
ZIP/Postal Code
432101228
Country
United States
Facility Name
Med College of Ohio
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43699
Country
United States
Facility Name
Milton S Hershey Med Ctr
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
170330850
Country
United States
Facility Name
Univ of Pennsylvania at Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson Univ Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191075098
Country
United States
Facility Name
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Vanderbilt Univ Med Ctr
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Univ of Texas Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
775550435
Country
United States
Facility Name
Wilford Hall Med Ctr
City
Lackland Air Force Base
State/Province
Texas
ZIP/Postal Code
782365300
Country
United States
Facility Name
Brooke Army Med Ctr
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284
Country
United States
Facility Name
Ramon Ruiz Arnau Univ Hosp / Pediatrics
City
Bayamon
ZIP/Postal Code
00956
Country
Puerto Rico
Facility Name
San Juan City Hosp
City
San Juan
ZIP/Postal Code
009367344
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
background
Citation
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)
Results Reference
background
PubMed Identifier
8843229
Citation
Holodniy M, Katzenstein D, Mole L, Winters M, Merigan T. Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. J Infect Dis. 1996 Oct;174(4):854-7. doi: 10.1093/infdis/174.4.854.
Results Reference
background

Learn more about this trial

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

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