randomized, phase i/ii, dose-ranging, open-label trial of the anti-hiv activity of delavirdine mesylate (dlv; u-90,152s)

Conditions: HIV Infections

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.

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.

Eligibility criteria:
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.

Keywords: didanosine acquired immunodeficiency syndrome aids-related complex antiviral agents zidovudine