A Comparison of Zidovudine (AZT) and Stavudine in HIV-Infected Patients

A Double-Blind Comparison of Zidovudine (AZT) Versus Stavudine (d4T; BMY 27857) for the Treatment of Patients With HIV Infection Who Have Absolute CD4 Lymphocyte Counts Between 50 and 500 Cells/mm3

To compare stavudine (d4T) and zidovudine (AZT) in slowing the progression of HIV disease. To compare the antiviral activity of d4T versus AZT as measured by plasma levels of p24 antigen and HIV viremia, and their relative efficacy by improvement and/or absence of adverse changes over time in laboratory parameters associated with HIV infection. To compare the safety of oral doses of d4T to AZT in patients with HIV infection.

Inclusion Criteria

Concurrent Medication:

Allowed:

• AZT.

Patients must have:

• Documented HIV infection as determined by a positive ELISA and/or Western blot.
• Absolute CD4 count of 100 - 500 cells/mm3 within 90 days prior to registration OR a CD4 count of 50 - 99 cells/mm3 within 30 days prior to registration.
• Prior zidovudine therapy for at least 6 months and currently tolerating at least 500 mg daily.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Newly diagnosed AIDS-defining opportunistic infection requiring acute therapy at time of enrollment.
• Need for chronic systemic therapy at time of enrollment.
• Intractable diarrhea.
• Signs or symptoms of bilateral peripheral neuropathy at time of screening.
• Demonstrated intolerance to zidovudine therapy.
• Any other clinical conditions that would render the patient unsuitable for study or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

• Chronic systemic therapy with agents likely to suppress bone marrow, cause neurotoxicity, or create hepatic dysfunction.

Patients with the following prior conditions are excluded:

• Prior history of bilateral peripheral neuropathy.
• Demonstrated intolerance to zidovudine therapy.

Prior Medication:

Excluded:

• Prior d4T, ddI, or ddC.
• Other investigational antiretroviral drugs (e.g., AZddU, Al 721, interferon, or immunomodulating drugs within 1 month prior to study entry or ribavirin within 3 months prior to study entry).
• Prior myelosuppressive, neurotoxic, or cytotoxic anticancer therapy within 3 months prior to study entry.
• Any prior therapy that would render the patient unsuitable for study or unable to comply with dosing requirements.

Required:

• At least 6 months of prior AZT and currently tolerating at least 500 mg daily, with the last dose received no more than 7 days prior to study entry.