HIV Infections
Conditions
Keywords
Didanosine, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine
Brief summary
PRIMARY: To study the safety and tolerance of delavirdine mesylate ( U-90152 ) monotherapy. To compare the anti-HIV activity of three blood concentration levels of this agent with nucleoside analog monotherapy, either zidovudine ( AZT ) or didanosine ( ddI ), based on the reduction of HIV viral burden. SECONDARY: To use pharmacokinetic parameters to assess the relationship between daily drug exposure and antiviral activity and toxicity of the U-90152, AZT, and ddI monotherapy. To assess anti-HIV activity using other disease markers. Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.
Detailed description
Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors. Patients are randomized to receive U-90152 at one of three doses (treatment arms I through III) or either AZT or ddI (treatment arm IV). Patients on arm IV who are AZT-naive receive AZT; those who are AZT-experienced receive ddI. Treatment continues for 24 weeks. PER 12/22/94 AMENDMENT: All patients receiving U-90152 have the same starting dose, to attain one of three target trough levels.
Interventions
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Concurrent Medication: Allowed: * PCP prophylaxis. * Topical antifungal agents, clotrimazole troches, nystatin oral suspension, topical ketoconazole, and oral fluconazole. * Acyclovir (\<= 1000 mg/day) as maintenance therapy for herpes simplex virus. * Recombinant erythropoietin and G-CSF. * Antibiotics for bacterial infections, unless specifically excluded. * Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics. * Antacids. Patients must have: * HIV-1 infection. * CD4 count 200 - 500 cells/mm3. * Either no prior antiretroviral therapy or discontinued AZT monotherapy 3 or more weeks prior to study entry. NOTE: * Half of patients should be antiretroviral naive. Prior Medication: Allowed: * Prior AZT.
Exclusion criteria
Co-existing Condition: Patients with the following symptoms or conditions are excluded: * Malignancy other than minimal Kaposi's sarcoma. Concurrent Medication: Excluded: * Rifabutin. * Rifampin. * Terfenadine. * Astemizole. * Loratadine. * Trifluoperazine. * Piperazine citrate. * Any acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection. * Non-study antiretroviral therapies, interferons, biologic response modifiers, and HIV vaccines. * Systemic corticosteroids for more than 21 consecutive days. * Foscarnet. * Systemic cytotoxic chemotherapy for a malignancy. Patients with the following prior conditions are excluded: * History of pancreatitis (in patients who received prior AZT). * History of grade 2 or worse peripheral neuropathy (in patients who received prior AZT). * History of hypersensitivity to BHAP compounds (e.g., trifluoperazine - Stelazine, piperazine citrate - Antepar). Prior Medication: Excluded within 30 days prior to study entry: * Any investigational medication. * Interferon. * Interleukin. * Rifabutin. * Rifampin. * Terfenadine. * Astemizole. * Loratadine. * Trifluoperazine. * Piperazine citrate. Excluded at any time: * Prior ddI, ddC, d4T, or 3TC. * Prior foscarnet. * Prior BHAP compound or other non-nucleoside RT inhibitor. Active substance abuse interfering with compliance.
Countries
United States
Outcome results
None listed