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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000831
• Other study ID #: ACTG 302
• Secondary ID: 11277
• Status: Completed
• Phase: Phase 2
• Est. completion date: May 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: May 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Lamivudine

• Stavudine

• Zidovudine

• Didanosine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico,  Tanzania, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation