A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Adefovir Dipivoxil When Added to Standard Antiretroviral Therapy for the Treatment of HIV-Infected Patients With CD4 Cell Counts >= 200/mm3

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Adefovir Dipivoxil When Added to Standard Antiretroviral Therapy for the Treatment of HIV-Infected Patients With CD4 Cell Counts >= 200/mm3

To evaluate the anti-HIV activity, safety, and tolerance of adefovir dipivoxil ( bis-POM PMEA ) in combination with standard antiretroviral therapy for 48 weeks.

Patients are randomized to receive either adefovir dipivoxil or placebo daily for 24 weeks, after which all patients will receive open-label drug for an additional 24 weeks. Study drug is administered in combination with a current antiretroviral regimen for the entire 48 weeks. Patients are followed every 4 weeks during the first 24 weeks of study, then every 8 weeks during the last 24 weeks.

Inclusion Criteria

Patients must have:

• HIV infection with HIV RNA titer >= 2500 copies/ml (2.5 KEq/ml) plasma.
• CD4 count >= 200 cells/mm3.
• No new AIDS-defining event within the past 2 months.
• Life expectancy at least 1 year.
• Consent of parent or guardian if less than 18 years old.
• Tolerated antiretroviral therapy for the past 2 months.

NOTE:

• Kaposi's sarcoma is permitted provided patient has not received systemic therapy within the past month.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Active, serious infections other than HIV that require parenteral antibiotic or antiviral therapy.
• Gastrointestinal malabsorption syndrome or chronic nausea or vomiting that would preclude oral medication.
• Malignancy other than Kaposi's sarcoma or basal cell carcinoma.

Concurrent Medication:

Excluded:

• Immunomodulating agents such as systemic corticosteroids, IL-2, or interferons.
• Isoniazid.
• Rifampin.
• Investigational agents (unless approved by sponsor).
• Systemic chemotherapeutic agents.

Prior Medication:

Excluded:

• Parenteral antibiotic or antiviral therapy for another active, serious infection within the past 2 weeks.
• Immunomodulating agents such as systemic corticosteroids, IL-2, or interferons within the past month.
• Systemic therapy for KS within the past month.

Required:

• Antiretroviral regimen other than study drug.

Required:

• Antiretroviral therapy for at least the past 2 months. Current alcohol or substance abuse that would interfere with compliance.