Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy - Full Text View

Study Description

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


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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	12 Years and older (Child, Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000831

Show 40 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Katzenstein D
Study Chair:	Hammer S

More Information

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 Key Record Dates
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