A Multicenter Phase II Double-Blind Exploratory Study to Evaluate Differences Among Various Zidovudine/Didanosine Regimens on Quantitative Measures of Viral Burden in Relatively Early HIV-1 Infection

A Multicenter Phase II Double-Blind Exploratory Study to Evaluate Differences Among Various Zidovudine/Didanosine Regimens on Quantitative Measures of Viral Burden in Relatively Early HIV-1 Infection

To determine the relative antiviral activity and safety of zidovudine ( AZT ) and didanosine ( ddI ) alone and in combination, as well as in various sequences of administration.

The relative efficacy of the approved antiretrovirals in early HIV-1 disease is unclear; thus, a study is needed to evaluate the ability of these various nucleoside analogs to limit pathogenicity.

The relative efficacy of the approved antiretrovirals in early HIV-1 disease is unclear; thus, a study is needed to evaluate the ability of these various nucleoside analogs to limit pathogenicity.

Patients undergo observation for 2 weeks, then are randomized to one of six treatment arms to receive ddI alone or in sequence or combination with AZT for 16-32 weeks, followed by 4 weeks of post-treatment evaluation. The regimens are: ddI alone for 32 weeks; AZT for 16 weeks followed by ddI for 16 weeks; AZT for 16 weeks followed by AZT/ddI combination for 16 weeks; ddI for 16 weeks followed by AZT for 16 weeks; AZT/ddI combination for 32 weeks; and placebo for 32 weeks.

PER AMENDMENT 6/18/96: NOTE: Patients enrolled under version 3 of the study will terminate treatment at week 16 and have a 4 week follow up.

Inclusion Criteria

Patients must have:

• HIV-1 seropositivity.
• CD4 count >= 550 cells/mm3.
• Asymptomatic disease.
• No prior antiretroviral therapy.
• Consent of parent or guardian if less than 18 years old.

PER AMENDMENT 6/18/96:

• Patients with an undocumented history of oral candidiasis or a history of candidiasis that was antibiotic associated may enroll.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Medical condition that precludes study compliance.

Concurrent Medication:

Excluded:

• Antiretrovirals other than study drugs.
• Biologic response modifiers including erythropoietin and G-CSF.
• Systemic corticosteroids.
• Systemic cytotoxic chemotherapy.
• Intravenous pentamidine.

Concurrent Treatment:

Excluded:

• Systemic radiation therapy.

Patients with the following prior conditions are excluded:

• History of grade 2 or worse peripheral neuropathy.
• History of pancreatitis or factors predisposing to pancreatitis.

Prior Medication:

Excluded:

• Prior antiretrovirals.
• Systemic immunomodulators (e.g., gp120, gp160, IL-2, interferons) within 3 months prior to study entry.

Chronic alcoholism.