To evaluate the safety and tolerance, in patients with severe clinical manifestations of HIV
infection, of zidovudine (AZT) administered daily for 48 weeks as a low dose every 4 hours or
a higher dose every 12 hours.
Inclusion Criteria
Concurrent Medication:
Allowed:
- Prophylaxis or treatment for Pneumocystis carinii pneumonia (PCP) consisting of either
trimethoprim / sulfamethoxazole, aerosolized pentamidine, pyrimethamine / sulfadoxine, or
dapsone allowed at the discretion of the investigator.
Patients with the following are excluded:
- Any immediately life-threatening infection or medical condition present at the time of
study entry.
- Any active opportunistic or other infection requiring chronic therapy at the time of
study entry. Patients with PCP may be randomized to study medication following a
minimum 7-day course of therapy resulting in stabilization of their disease. Patients
with stabilized disease must have a fever < 39 C for at least 48 hours, pO2 (on room
air ) = or > 60 mm, and an Arterial/alveolar gradient = or < 30 mm.
- Diagnosis of AIDS Dementia Complex.
- Received more than 4 weeks of antiretroviral therapy or who previously discontinued
antiretroviral therapy due to drug related toxicity.
- Diseases and conditions listed in Exclusion Co-existing Conditions.
Patients must have the following:
- Seropositive for HIV infection documented by any federally licensed ELISA and
confirmed by Western blot.
- Advanced HIV disease or AIDS-related complex.
- Ability to give informed consent.
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions or symptoms are excluded:
- AIDS with malignant disease likely to require cytotoxic chemotherapy.
- Diagnosis of AIDS Dementia Complex.
- Impaired renal function ( Creatinine clearance < 50 ml/min/1. 73m2 or serum creatinine
= or > 2 mg/dl).
- Impaired hepatic function ( ALT = or > 5 x upper limit of normal).
- Fever > 39 C at entry.
Concurrent Medication:
Excluded:
- Any other experimental therapy.
- Drugs which cause significant bone marrow suppression.
- Cytolytic chemotherapy.
- Drugs which cause significant nephrotoxicity or hepatotoxicity.
Concurrent Treatment:
Excluded:
- Radiation therapy (with the exception of electron beam therapy to an area < 100 cm2).
Prior Medication:
Excluded within 2 weeks of study entry:
- Any other experimental therapy. Drugs which cause significant bone marrow suppression.
Cytolytic chemotherapy. Drugs which cause significant nephrotoxicity or hepatotoxicity.
Excluded within 4 weeks of entry:
- Immunomodulating agents, including pharmacological doses of steroids for more than 10
days (except for management of severe PCP in which case duration should not exceed 21
days). Interferon. Isoprinosine. IL-2.
Excluded within 8 weeks of entry:
-
Antiretroviral agents including:
- Ribavirin. Dideoxycytidine (ddC). Dideoxyadenosine (ddA). Didanosine (ddI). Foscarnet.
Dextran Sulfate. AL-721. Retrovir (Zidovudine, AZT) for greater than 4 weeks or within 90
days of study entry, or patients who originally discontinued Retrovir due to drug-related
toxicity. Drugs metabolized by hepatic glucuronidation may alter the metabolism of Retrovir
and should not be used chronically.
Prior Treatment:
Excluded:
- Radiation therapy (with the exception of electron beam therapy to an area < 100 cm2)
within 2 weeks of study entry.
Known active drug or alcohol abuse.
San Juan Veterans Administration Med Ctr, San Juan 009275800, Puerto Rico
Univ of Arizona / Health Science Ctr, Tucson, Arizona 85724, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Missouri at Kansas City School of Medicine, Kansas City, Missouri 64108, United States
North Jersey Community Research Initiative, Newark, New Jersey 071032842, United States
Univ of New Mexico Hlth Sciences Ctr / Dept of Med, Albuquerque, New Mexico 87131, United States
Northshore Hosp / Cornell Univ, Manhasset, New York 11030, United States
Univ of Pennsylvania / HIV Clinic, Philadelphia, Pennsylvania 19104, United States
Univ TX Galveston Med Branch, Galveston, Texas 77550, United States
Baylor College of Medicine, Houston, Texas 77030, United States
