A Randomized, Double-Blind Study of MKC-442 Combined With Viracept in Patients Who Are Epivir + Retrovir Experienced and Are Protease Inhibitor- and Non-Nucleoside Reverse Transcriptase Inhibitor-Naive

Inclusion Criteria Concurrent Medication: Required: At least 1 different nucleoside analog, e.g., 3TC, d4T, or ddI (excluding zidovudine). Allowed: Chemoprophylaxis for Pneumocystis carinii pneumonia. Short courses (less than 21 days) of acyclovir for acute treatment. Recombinant erythropoietin or G-CSF for Grade 3 or greater anemia and neutropenia, respectively. Allowed only with caution and close patient monitoring: Ketoconazole, fluconazole, itraconazole, and grapefruit juice. Medications metabolized by cytochrome P450. Oral contraceptives, contraceptive implants such as Norplant, or injection-type contraceptives such as Depo-Provera only if not sole method of contraception. Patients may have: HIV-1 RNA greater than 10,000. No active AIDS-defining illnesses. Prior experience with 2 nucleoside analogues and able to switch to at least 1 different non-nucleoside analog, e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI) with HIV-1 RNA 10,000 copies/ml or less. [AS PER: 8/4/98 AMENDMENT]. [AS PER AMENDMENT 8/4/98: Nucleoside analog-naive patients must have HIV-1 RNA greater than 50,000 copies/ml.]. Prior Medication: Allowed: Treatment with 2 nucleoside analogs. Note: able to switch to at least 1 different nucleoside analog e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI), while on study [AS PER AMENDMENT 8/4/98]. Exclusion Criteria Co-existing Condition: Patients with any of the following symptoms or conditions are excluded: Active AIDS-defining illnesses. Malabsorption syndrome or severe chronic diarrhea within 30 days of entry, or inability to consume adequate oral intake due to chronic nausea, emesis, or abdominal or esophageal discomfort. [AS PER AMENDMENT 8/4/98]. Inadequately controlled seizure disorder [AS PER AMENDMENT 8/4/98]. Any intercurrent illness that could affect viral load determination [AS PER AMENDMENT 8/4/98]. Concurrent Medication: Excluded: Zidovudine. Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98]. Rifampin, rifabutin, phenobarbital, and hydantoin. Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride. Neurotoxic agents (e.g., vincristine, thalidomide). [AS PER AMENDMENT 8/4/98]. Patients with the following prior conditions are excluded: History of acute or chronic pancreatitis. History of > grade 2 peripheral neuropathy. Patients with an acute and clinically significant medical event within 30 days of screening. Prior Medication: Excluded: Protease inhibitors. Non-nucleoside reverse transcriptase inhibitors. Excluded within 30 days of study drug administration: Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98]. Rifampin, rifabutin, phenobarbital, and hydantoin. Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride. Immunotherapeutic vaccines. Cytotoxic chemotherapeutic agents [AS PER AMENDMENT 8/4/98]. Prior Treatment: Excluded within 30 days of study drug administration: Radiation therapy [AS PER AMENDMENT 8/4/98]. Risk Behavior: Excluded: Current alcohol or illicit drug use that, in the opinion of the investigator, may interfere with ability of patient to comply with dosing schedule and protocol evaluations.