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Comparison of Three Anti-HIV Drug Combinations in HIV-Infected Patients With No Symptoms of the Disease
This study has been completed.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001045
  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 II

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Didanosine Nevirapine
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

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

Estimated Enrollment: 300
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001045

  Show 59 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: Merigan TC
Study Chair: Mayers DL
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site
Click here for more information about Nevirapine  This link exits the ClinicalTrials.gov site

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.

Study ID Numbers: ACTG 244
Study First Received: November 2, 1999
Last Updated: July 29, 2008
ClinicalTrials.gov Identifier: NCT00001045  
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Virus Diseases
Nevirapine
Sexually Transmitted Diseases, Viral
Didanosine
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009