Purpose:
Primary: To compare the efficacy of zidovudine ( AZT ) given alone versus AZT plus
didanosine ( ddI ) versus AZT plus zalcitabine ( dideoxycytidine; ddC ) in delaying the
occurrence of AIDS-related conditions in HIV-infected patients.
Secondary: To compare the frequency and severity of adverse experiences in the three
regimens. To compare the mortality rates in the three regimens. To compare the effects of
antiretroviral regimens on CD4+ cell levels.
Studies have indicated that maintenance therapy with AZT over extended periods may be
limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of
drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or
ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of
development of drug-resistant strains, than AZT alone.
Study summary:
Studies have indicated that maintenance therapy with AZT over extended periods may be
limited by dose-dependent toxicity, primarily myelosuppression, and by the emergence of
drug-resistant HIV strains. It is anticipated that the combination of AZT with either ddI or
ddC may promote higher antiviral efficacy, with acceptable toxicity and less likelihood of
development of drug-resistant strains, than AZT alone.
Approximately 1200 patients are randomized in a 2:1:1:2 ratio to one of the following four
treatment arms: AZT plus ddI, AZT plus ddI placebo, AZT plus ddC placebo, and AZT plus ddC.
Average follow-up is 2 years.
Criteria:
Inclusion Criteria
Required:
- Documented HIV infection OR working diagnosis of HIV OR evidence of idiopathic
suppression with an AIDS-defining opportunistic infection or malignancy (except
Kaposi's sarcoma).
- CD4+ cell count = or < 200/mm3 or = or < 15 percent of total lymphocyte count within
previous 90 days OR history of AIDS-defining opportunistic infection.
- Current PCP prophylaxis.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
- Symptoms of pancreatitis or peripheral neuropathy of grade 2 or worse.
- Requirement for acute therapy for any active AIDS-defining opportunistic infection or
systemic chemotherapy for malignancy.
- Stage 2 or worse (moderate) AIDS Dementia Complex.
- Other disorders or conditions for which the study drugs are contraindicated or that
may prevent adequate compliance with study therapy.
Concurrent Medication:
Excluded:
- Acute therapy for active AIDS-defining opportunistic infection.
- Systemic chemotherapy for malignancy.
- Antiretroviral therapy other than that provided by this study.
Patients with the following prior conditions are excluded:
- History of pancreatitis or peripheral neuropathy of grade 2 or worse.
- History of intolerance to the study drugs at entry doses and/or frequencies.
- History of phenylketonuria.