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

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Nevirapine (Drug); Zidovudine (Drug); Didanosine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Merigan TC, Study Chair
Mayers DL, Study Chair

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.

Clinical Details

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 design: Primary Purpose: 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.

Eligibility

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, Puerto Rico

San Juan City Hosp, San Juan 009367344, Puerto Rico

UCLA CARE Ctr, Los Angeles, California 90095, United States

Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium, San Jose, California 951282699, United States

San Mateo AIDS Program / Stanford Univ, Stanford, California 943055107, United States

Stanford Univ Med Ctr, Stanford, California 943055107, United States

Harbor UCLA Med Ctr, Torrance, California 90502, United States

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States

George Washington Univ / Hershey Med Ctr, Washington, District of Columbia 20037, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States

Walter Reed Army Med Ctr, Washington, District of Columbia 20307, United States

Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta, Georgia 303652225, United States

Emory Univ Hosp / Pediatrics, Atlanta, Georgia 30306, United States

Queens Med Ctr, Honolulu, Hawaii 96816, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States

Natl Naval Med Ctr, Bethesda, Maryland 208995000, United States

Fitzsimmons Army Med Ctr, Rockville, Maryland 20850, United States

Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States

Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States

Univ of Minnesota, Minneapolis, Minnesota 55455, United States

St Paul Ramsey Med Ctr, St Paul, Minnesota 55101, United States

Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States

Adirondack Med Ctr at Saranac Lake, Albany, New York 122083479, United States

Albany Med College / Division of HIV Medicine A158, Albany, New York 122083479, United States

Mid - Hudson Care Ctr, Albany, New York 122083479, United States

Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States

Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States

Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States

Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States

Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States

North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States

SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Columbia Presbyterian Med Ctr, New York, New York 100323784, United States

Harlem Hosp Ctr, New York, New York 10037, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

SUNY / State Univ of New York, Syracuse, New York 13210, United States

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Carolinas Med Ctr, Charlotte, North Carolina 28203, United States

Wake County Dept of Health, Raleigh, North Carolina 27610, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States

Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States

Med College of Ohio, Toledo, Ohio 43699, United States

Milton S Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States

Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville, Tennessee 37920, United States

Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States

Univ of Texas Galveston, Galveston, Texas 775550435, United States

Wilford Hall Med Ctr, Lackland AFB, Texas 782365300, United States

Brooke Army Med Ctr, San Antonio, Texas 78284, United States

Additional Information

Click here for more information about Zidovudine

Click here for more information about Didanosine

Click here for more information about Nevirapine

Related 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)

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.


Last updated: March 30, 2012

Page last updated: August 23, 2015

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