A Study of 1592U89 in Combination With Protease Inhibitors in HIV-Infected Patients Who Have Never Taken Anti-HIV Drugs

An Open-Label, Phase II Trial to Evaluate the Steady-State Pharmacokinetics, Safety, and Efficacy of 1592U89 in Combination With Selected HIV-1 Protease Inhibitors in Antiretroviral-Naive, HIV-1-Infected Patients.

The purpose of this study is to see if it is safe and effective to give 1592U89 plus certain protease inhibitors (PIs) to HIV-infected patients who never have been treated with anti-HIV drugs. This study also examines how the body processes these drugs when they are given together.

In this Phase II, open-label study patients (16 per treatment group) are randomized to receive 1592U89 in combination with one of five protease inhibitors: indinavir, saquinavir, ritonavir, nelfinavir, or 141W94 for up to 48 weeks.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Local treatment for Kaposi's sarcoma.
• GM-CSF, G-CSF or erythropoietin.

Patients must have:

• HIV-1 infection documented by a licensed HIV-1 antibody ELISA and confirmed by Western blot detection of HIV-1 antibody or a positive HIV-1 blood culture.
• CD4+ cell count >= 100 cells/mm3 within 14 days of study drug administration.
• HIV-1 RNA >= 5,000 copies/ml within 14 days of study drug administration.
• No active or ongoing AIDS-defining opportunistic infection or disease.
• Signed, informed consent from parent or legal guardian for patients less than 18 years of age.

Prior Medication:

Allowed:

Local treatment for Kaposi's sarcoma.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Malabsorption syndrome, or other gastrointestinal dysfunction, that might interfere with drug absorption or render the patient unable to take oral medication.
• Life-threatening infection or other serious medical condition that may compromise a patient's safety.

Concurrent Medication:

Excluded:

• Other investigational agents. NOTE:
• Those available through Treatment IND or expanded access programs are evaluated individually.
• Chemotherapeutic agents for the initial 24 weeks of study (except local treatment for Kaposi's sarcoma).
• Agents with documented anti-HIV activity in vitro.
• Foscarnet.
• Immunomodulating agents such as systemic corticosteroids, interleukins, thalidomide, anti-cytokine agents or interferons.
• Antioxidants.

Concurrent Treatment:

Excluded:

Radiation therapy within the first 24 weeks of study.

Patients with the following prior conditions are excluded:

• History of clinically relevant pancreatitis or hepatitis within the last 6 months.
• Participation in an investigational HIV-1 vaccine trial.

Prior Medication:

Excluded:

• Antiretroviral therapy, including reverse transcriptase inhibitor and protease inhibitor therapy.
• Cytotoxic chemotherapeutic agents within 30 days of study drug administration.
• HIV-1 vaccine dose within the 3 months prior to study drug administration.
• Immunomodulating agents, such as systemic corticosteroids, interleukins or interferons within 30 days of study drug administration.

Prior Treatment:

Excluded:

Radiation therapy within 30 days of study drug administration. Alcohol or illicit drug use that may interfere with patient compliance.