The Safety and Effectiveness of PMPA Prodrug in HIV-Infected Patients

Inclusion Criteria Patients must have: HIV infection, as indicated by seropositivity for HIV infection (ELISA and Western blot), positive HIV culture, or positive plasma HIV RNA. CD4 cell count of 200 or more cells/mm3 within 28 days prior to study entry. Plasma HIV RNA of 10,000 or more copies/ml within 28 days of study entry. Minimum life expectancy of 12 months. Exclusion Criteria Co-existing Condition: Patients with any of the following symptoms or conditions are excluded: Active, serious infections (other than HIV infection) that require parenteral antibiotic therapy. Patients should be considered recovered if at least 2 weeks have elapsed following the cessation of parenteral antibiotic therapy before enrollment. Active clinically significant medical problems including cardiac disease (e.g., symptoms of ischemia, congestive heart failure, or arrhythmia). Positive test for Hepatitis B surface antigen (HBsAg). Malignancy other than basal cell carcinoma or cutaneous Kaposi's sarcoma. Prior Medication: Excluded: Adefovir dipivoxil (bis-POM PMEA) for more than 14 days. Within 2 weeks prior to entry: Antiretroviral therapy, including nucleoside analogues, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational antiretroviral agents. Interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, diuretics, foscarnet, ganciclovir, itraconazole, fluconazole, ketoconazole (topical allowed), isoniazid, rifampin, rifabutin, clarithromycin, azithromycin, systemic chemotherapeutic agents, systemic corticosteroids, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and other investigational agents. Risk Behavior: Excluded: Active drug or alcohol abuse as demonstrated by a positive screening test for drugs of abuse (except marijuana or drugs used for medical indications) or substance abuse considered sufficient to hinder patient compliance. Patients who are receiving: Antiretroviral therapy, including nucleoside analogues, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, or investigational antiretroviral agents. NOTE: Antiretroviral therapy may be started after completion of the Day 49 follow-up visit (i.e., not earlier than 14 days after completion of dosing). Interferon (alpha, beta, or gamma) or interleukin (e.g., IL-2) therapy, aminoglycoside antibiotics, amphotericin B, cidofovir, diuretics, foscarnet, ganciclovir, itraconazole, fluconazole, ketoconazole (topical allowed), isoniazid, rifampin, rifabutin, clarithromycin, azithromycin, systemic chemotherapeutic agents, systemic corticosteroids, other agents with significant nephrotoxic potential, other agents with significant nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and other investigational agents.