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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Stavudine; Drug: Zidovudine; Drug: Lamivudine; Drug: Didanosine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00000831

ACTG 302

11277 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.