A Comparison of Two Dose Levels of Didanosine Used in Combination With Stavudine in HIV-Infected Patients

A Randomized, Double-Blind Study of the Antiviral Activity of Once-Daily and Twice-Daily Dosing of Didanosine in Combination With Twice-Daily Dosing of Stavudine in HIV-Infected Subjects

The purpose of this study is to compare the effectiveness of taking didanosine (ddI) once a day plus stavudine (d4T) twice a day with taking ddI twice a day plus d4T twice a day. This study also examines the safety of giving ddI with d4T in the short-term.

Patients are randomized to receive ddI given either qd or bid in combination with d4T given bid (no doses specified).

Inclusion Criteria

Patients must have:

• Documented HIV infection.
• CD4 cell count of at least 100 cells/mm3.
• Plasma HIV RNA count of 10,000 copies/ml or more within 14 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

• Presence of a newly diagnosed AIDS-defining opportunistic infection requiring acute therapy at the time of enrollment.
• Bilateral peripheral neuropathy or signs and symptoms of bilateral peripheral neuropathy greater than or equal to Grade 2 at the time of screening.
• Inability to tolerate oral medication.
• Any other clinical condition that would preclude compliance with dosing requirements.

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.

• Intractable diarrhea (6 or more loose stools/day for more than 7 consecutive days) within 30 days prior to study entry.

• Proven or suspected acute hepatitis within 30 days prior to study entry.

  1. Potent neurotoxic drugs, such as vincristine and thalidomide.

• Other anti-HIV therapy.

  1. Prophylaxis for pneumocystis carinii pneumonia (PCP) is strongly recommended for patients with CD4 cell counts less than or equal to 200/mm3 or who have had a prior episode of PCP.

• Immunizations recommended by ACIP for routine practice.

• Erythropoietin and G-CSF are allowed if myelosuppression emerges on study.

  1. Any antiretroviral therapy.

• Agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 3 months of study entry.

  1. Any prior antiretroviral therapy.

• Agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic potential within 3 months of study entry.

Active alcohol or substance abuse that would prevent adequate compliance or would increase the risk of pancreatitis.