To evaluate the pharmacokinetics of Retrovir (AZT) administered orally as 1 of 3 doses in the
treatment of patients with severe clinical and laboratory manifestations of HIV infection. To
compare the safety and tolerance of AZT administered 2, 3, and 6 x daily to these patients.
Inclusion Criteria
Concurrent Treatment:
Allowed:
- Electron beam therapy to an area of less than 100 cm2.
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 present at the
time of study entry.
- Patients with Pneumocystis carinii pneumonia (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 fever < 39 degrees C for at
least 48 hours; oxygen (on room air)
= or > 60 mm, and arterial / alveolar gradient = or < 30 mm.
- Kaposi's sarcoma, lymphoma, or other tumor likely to require cytotoxic chemotherapy.
Seropositive for HIV antibody documented by any federally licensed ELISA.
Patients must have ability to give informed consent and advanced HIV disease defined as:
- History of Pneumocystis carinii pneumonia (PCP) with histologic verification within 4
months of study entry.
OR History of other opportunistic infection included in the CDC surveillance definition of
AIDS (stage IV-C-1), diagnosed within 4 months of entry, but not requiring chronic
suppressive therapy, and a CD4+ cell count < 200 cells/mm3.
OR AIDS related complex (ARC) only those patients with a CD4+ count < 200 cells/mm3 and
documentation of at least two signs or symptoms from the list below. One sign or symptom
must be weight loss or candidiasis as described.
- Unexplained weight loss > 10 percent or = or > 15 lbs within the previous 4 months;
with low weight at entry.
- History of mucocutaneous oral candidiasis (by culture or potassium hydroxide KOH
smear).
- Fever > 38 degrees C, without documented infectious cause present, persisting > 1
month.
- Oral hairy leukoplakia.
- Unexplained night sweats, persisting > 1 month.
- Herpes zoster infection within 3 months of entry.
- Chronic diarrhea of unknown infectious etiology persisting > 1 month after 3 samples
have been done eliminating ova, parasites, Cryptosporidia, Mycobacterium avium
intracellulare, cytomegalovirus (CMV), and other pathogens associated with diarrheal
disease in AIDS patients.
Negative Venereal Disease Research Laboratory (VDRL) or Rapid Plasma Reagent (RPR) or, if
positive and verified by Fluorescent Treponemal Antibody Absorption (FTAABS), documented
history of treatment for syphilis. If FTAABS is positive, but treatment history is not
available, the patient may be entered 3 or more days following the initiation of
appropriate chemotherapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following are excluded:
- Chronic herpes virus infection.
- Fever > 39 degrees C at study entry.
- Known hypersensitivity to lactate and/or gelatin.
- Kaposi's sarcoma, lymphoma, or other tumor likely to require cytotoxic chemotherapy.
- Impaired renal function.
- AIDS dementia complex.
Concurrent Medication:
Excluded:
- Drugs which cause significant bone marrow suppression.
- Rifampin or rifampin derivatives.
- Drugs which cause significant nephrotoxicity or hepatotoxicity.
- Antiretroviral agents, including ribavirin, dideoxycytidine, dideoxyadenosine,
didanosine, foscarnet, dextran sulfate, and AL-721.
- Acyclovir therapy of more than 21 days duration.
Concurrent Treatment:
Excluded:
- Radiation therapy (with the exception of electron beam therapy to an area of less than
100 cm2).
- Experimental therapy.
- Cytolytic chemotherapy.
Prior Medication:
Excluded:
- Acyclovir therapy of more than 21 days duration.
- Zidovudine (AZT).
- Excluded within 2 weeks of study entry:
- Drugs which cause significant bone marrow suppression.
- Rifampin or rifampin derivatives.
- Drugs which cause significant nephrotoxicity or hepatotoxicity.
- Immunomodulating agents, including pharmacologic doses of steroids for > 10 days.
- Excluded within 4 weeks of study entry:
- Interferon.
- Isoprinosine.
- IL-2.
- Excluded within 8 weeks of study entry:
- Antiretroviral agents, including ribavirin, dideoxycytidine, dideoxyadenosine,
didanosine, foscarnet, dextran sulfate, and AL-721.
Prior Treatment:
Excluded:
- Radiation therapy (with the exception of electron beam therapy to an area of less than
100 cm2).
- Experimental therapy.
- Cytolytic chemotherapy.
Active drug or alcohol abuse.
Univ of Arizona / Health Science Ctr, Tucson, Arizona 85724, 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
Johns Hopkins Hosp, Baltimore, Maryland 21205, United States
Univ of Missouri at Kansas City School of Medicine, Kansas City, Missouri 64108, 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
Baylor College of Medicine, Houston, Texas 77030, United States
Univ TX Galveston Med Branch, Galveston, Texas 77550, United States
