Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on May 09, 2007
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Lamivudine (Drug); Stavudine (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):
Katzenstein D, Study Chair
Hammer S, Study Chair
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.
Clinical Details
Official title:
Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy
Study design: Interventional, Treatment
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.
Eligibility
Minimum age: 12 Years.
Gender(s): Both.
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.
Locations and Contacts
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Children's Hosp of Los Angeles, Los Angeles, California 90027, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Mountain States Reg Hemo Ctr / Univ of Colorado, Denver, Colorado 80262, United States
George Washington Univ / Hershey Med Ctr, Washington, District of Columbia 20037, United States
Georgetown Univ Hosp, Washington, District of Columbia 20037, United States
Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta, Georgia 303652225, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Great Plains - Hemophilia / Univ of Iowa Hosp & Clinic, Iowa City, Iowa 52242, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester, Massachusetts 01605, United States
Michigan State Univ Hemophilia Comprehensive Care Clinic, Lansing, Michigan 48912, United States
St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Robert Wood Johnson Med School / Hershey Med Ctr, New Brunswick, New Jersey 08903, United States
SUNY / State Univ of New York, Syracuse, New York 13210, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Mount Sinai Med Ctr / Hemophilia Treatment Ctr, New York, New York 10029, United States
Carolinas Med Ctr, Charlotte, North Carolina 28203, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Milton S Hershey Med Ctr, Hershey, Pennsylvania 170330850, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ Texas Health Science Ctr / Univ Texas Med School, Houston, Texas 77030, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Didanosine Click here for more information about Stavudine Click here for more information about Lamivudine
Related publications: Shulman N, Shafer R, Winters M, Machekano R, Liou S, Hughes M, Zolopa A, Katzenstein D. Genotypic predictors of virologic response to stavudine after zidovudine monotherapy (ACTG 302). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 437) Shulman NS, Machekano RA, Shafer RW, Winters MA, Zolopa AR, Liou SH, Hughes M, Katzenstein DA. 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.
Last updated: June 23, 2005
|
