Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy

Study Description

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Brief Summary:

To elucidate the relationship between virologic risk factors and immunologic and clinical progression in patients receiving monotherapy in protocol ACTG 175, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. Specifically, to determine, in patients who have been taking zidovudine (AZT) alone for a long time, whether it is beneficial to add lamivudine (3TC) to AZT or to switch to d4T alone, and also to determine, in patients who have been taking didanosine (ddI) alone for a long time, whether it is beneficial to add AZT or AZT/3TC to ddI.

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Lamivudine; Drug: Stavudine; Drug: Zidovudine; Drug: Didanosine	Phase 2

Detailed Description:

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Patients with prior AZT experience only are randomized to receive either d4T alone or AZT/3TC. Patients with prior ddI experience only are randomized to receive ddI/AZT or ddI/AZT/3TC. PER AMENDMENT 8/27/96: The study has been extended 6 months and treatment will be available until March 15, 1997 at the latest. Each patient will have regularly scheduled 12 week safety visits during the extension period.

AS PER AMENDMENT 1/22/97: The study has been extended for approximately 16 additional weeks beyond the current 6-month extension. Subjects will be unblinded to their assigned regimen beginning 2/21/97 and will continue therapy for up to 16 weeks in open-label fashion. AS PER AMENDMENT 5/9/97: The study has been extended for an additional 8 weeks; study drug will not be provided after 9/15/97.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	280 participants
Primary Purpose:	Treatment
Official Title:	Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy
Actual Study Completion Date :	May 1998

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis in patients with CD4 count <= 200 cells/mm3.

Allowed:

• Chemophylaxis against Mycobacterium tuberculosis.
• Acyclovir.
• Vaccination with pneumococcal vaccine polyvalent.
• Haemophilus B Conjugate vaccine.
• Chemoprophylaxis for MAC and Toxoplasma gondii.
• Antibiotics.
• Recombinant erythropoietin ( EPO ) and G-CSF.
• Systemic corticosteroids for < 21 days.
• Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, and oral contraceptives.
• Vitamins and herbal therapies.

Concurrent Treatment:

Allowed:

• Limited local radiation therapy to skin.
• Blood transfusions if 3 units or less per 21-day period.
• Acupuncture.
• Visualization techniques.

Patients must have:

• Completed AZT or ddI monotherapy on ACTG 175 and remained on that regimen during any subsequent interval.
• Not reached an ACTG 175 endpoint prior to May 1, 1995.
• Consent of parent or guardian if less than 18 years old.

PER AMENDMENT 8/27/96:

• Patients must be on study/on treatment at the time the protocol study treatment is extended.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Grade 2 or worse peripheral neuropathy.
• Malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

• Anti-HIV drugs other than study drugs.
• Biologic response modifiers.
• Systemic cytotoxic chemotherapy.
• Any drug known to affect glucuronidation and/or clearance of AZT.

Concurrent Treatment:

Excluded:

• Radiation therapy other than limited local therapy to skin.

Patients with the following prior condition are excluded:

• History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

• Prior 3TC.
• Acute therapy for an infection (other than HIV) or other medical illness within 14 days prior to study entry.

Current ethanol abuse.

Contacts and Locations

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Locations

United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States
United States, California
USC CRS
Los Angeles, California, United States, 90033
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
Stanford CRS
Palo Alto, California, United States, 94305
Ucsd, Avrc Crs
San Diego, California, United States, 92103
Ucsf Aids Crs
San Francisco, California, United States
Santa Clara Valley Med. Ctr.
San Jose, California, United States
San Mateo County AIDS Program
San Mateo, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States
United States, Georgia
Emory Univ. Hemophilia Program Office
Atlanta, Georgia, United States, 30365
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Hemophilia Treatment Ctr.
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St. Louis, Missouri, United States
United States, Nebraska
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States, 10021
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, United States, 28203
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Puerto Rico
Puerto Rico-AIDS CRS
San Juan, Puerto Rico
Tanzania
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, Tanzania

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Katzenstein D
Study Chair:	Hammer S

More Information

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Publications:

Shulman NS, Machekano RA, Shafer RW, Winters MA, Zolopa AR, Liou SH, Hughes M, Katzenstein DA; AIDS Clinical Trials Group 302 Study Team. Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):377-80.

Katzenstein DA, Hughes M, Albrecht M, Hammer S, Para M, Murphy R, Valdez H, Haubrich R, Liou S. Virologic and CD4+ cell responses to new nucleoside regimens: switching to stavudine or adding lamivudine after prolonged zidovudine treatment of human immunodeficiency virus infection. ACTG 302 Study Team. AIDS Clinical Trials Group. AIDS Res Hum Retroviruses. 2000 Jul 20;16(11):1031-7.

Shulman NS, Hughes MD, Winters MA, Shafer RW, Zolopa AR, Hellmann NS, Bates M, Whitcomb JM, Katzenstein DA. Subtle decreases in stavudine phenotypic susceptibility predict poor virologic response to stavudine monotherapy in zidovudine-experienced patients. J Acquir Immune Defic Syndr. 2002 Oct 1;31(2):121-7.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000831 History of Changes
Other Study ID Numbers:	ACTG 302; 11277 ( Registry Identifier: DAIDS ES Registry Number )
First Posted:	August 31, 2001
Last Update Posted:	May 2, 2012
Last Verified:	May 2012

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

Didanosine; Drug Therapy, Combination; AIDS-Related Complex; Antiviral Agents	Zidovudine; Stavudine; Lamivudine; Drug Combinations

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lamivudine; Zidovudine	Stavudine; Didanosine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; Antimetabolites