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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001045
• Other study ID #: ACTG 244
• Secondary ID: 11221
• Status: Completed
• Phase: Phase 2
• Est. completion date: October 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: October 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Nevirapine

• Zidovudine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
United States	Adirondack Med Ctr at Saranac Lake	Albany	New York
United States	Albany Med College / Division of HIV Medicine A158	Albany	New York
United States	Mid - Hudson Care Ctr	Albany	New York
United States	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	State of MD Div of Corrections / Johns Hopkins Univ Hosp	Baltimore	Maryland
United States	Natl Naval Med Ctr	Bethesda	Maryland
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York
United States	Comprehensive Health Care Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Jack Weiler Hosp / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Family Health Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York
United States	Montefiore Med Ctr Adolescent AIDS Program	Bronx	New York
United States	North Central Bronx Hosp / Bronx Municipal Hosp	Bronx	New York
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Carolinas Med Ctr	Charlotte	North Carolina
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	MetroHealth Med Ctr	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Univ of Texas Galveston	Galveston	Texas
United States	Milton S Hershey Med Ctr	Hershey	Pennsylvania
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Univ of Iowa Hosp and Clinic	Iowa City	Iowa
United States	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee
United States	Wilford Hall Med Ctr	Lackland Air Force Base	Texas
United States	UCLA CARE Ctr	Los Angeles	California
United States	Hennepin County Med Clinic	Minneapolis	Minnesota
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Wake County Dept of Health	Raleigh	North Carolina
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Fitzsimmons Army Med Ctr	Rockville	Maryland
United States	St Paul Ramsey Med Ctr	Saint Paul	Minnesota
United States	Brooke Army Med Ctr	San Antonio	Texas
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	SUNY / State Univ of New York	Syracuse	New York
United States	Med College of Ohio	Toledo	Ohio
United States	Harbor UCLA Med Ctr	Torrance	California
United States	Children's Hosp of Washington DC	Washington	District of Columbia
United States	George Washington Univ / Hershey Med Ctr	Washington	District of Columbia
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Walter Reed Army Med Ctr	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb, Glaxo Wellcome

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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. — View 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)

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)