a phase ii double-blind study of delavirdine mesylate ( u-90152 ) in combination with zidovudine ( azt ) and/or didanosine ( ddi ) versus azt and ddi combination therapy

Conditions: HIV Infections

Summary: to determine the safety and anti-hiv activity of delavirdine mesylate ( u-90152 ) in combination with zidovudine ( azt ) and/or didanosine ( ddi ) versus azt/ddi combination. u-90152 has demonstrated anti-hiv activity. since the combination of this drug with either azt or ddi has synergistic inhibitory activity against hiv-1 in vitro, and triple therapy appears to have greater inhibitory activity against hiv-1 in vitro than dual therapy, the use of u-90152 in combination with azt and/or ddi may improve the benefits of these drugs in persons with hiv disease.

u-90152 has demonstrated anti-hiv activity. since the combination of this drug with either azt or ddi has synergistic inhibitory activity against hiv-1 in vitro, and triple therapy appears to have greater inhibitory activity against hiv-1 in vitro than dual therapy, the use of u-90152 in combination with azt and/or ddi may improve the benefits of these drugs in persons with hiv disease. patients are randomized to receive u-90152/azt/ddi, u-90152/azt, u-90152/ddi, or azt/ddi for 48 weeks.

Eligibility criteria:
inclusion criteria concurrent medication: required: * pcp prophylaxis for patients with cd4 count \<= 200 cells/mm3. allowed: * topical antifungal agents. * oral ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections. * isoniazid, ethambutol, pyrazinamide, clofazimine, ciprofloxacin, and clarithromycin for acute or maintenance therapy for mycobacterial disease (also clarithromycin for mac prophylaxis). * acute or maintenance therapy for toxoplasmosis. * acute or maintenance therapy with acyclovir (no more than 1000 mg/day) for herpes simplex virus infection. * repo and rg-csf. * antibiotics for bacterial infections (except rifampin and rifabutin). * antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and methadone. concurrent treatment: allowed for cutaneous kaposi's sarcoma: * localized radiation therapy. * limited intralesional therapy. patients must have: * hiv infection. * cd4 count 100 - 500 cells/mm3. * prior cumulative monotherapy of \<= 6 months (may have taken either azt or ddi, but not both) or no prior antiretroviral therapy. exclusion criteria co-existing condition: patients with the following symptoms or conditions are excluded: * malignancy (other than basal or squamous cell carcinoma of the skin, stage 1 or 2 cervical intraepithelial neoplasia, or minimal kaposi's sarcoma). * considered to be unlikely to comply with study requirements. concurrent medication: excluded: * antiretroviral therapies and biologic response modifiers (except for study medications, repo, and rg-csf). * rifampin. * rifabutin. * terfenadine. * astemizole. * loratadine. * quinidine. * digitoxin. * 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 intolerance to azt at \<= 600 mg/day or ddi at \<= 400 mg/day or discontinuation of either drug for toxicity. * history of intolerance to trifluoperazine or piperazine citrate (per amendment). * history of pancreatitis. * history of grade 2 or worse peripheral neuropathy. * unexplained temperature \>= 38.5 c on any 7 days within the past 30 days. * chronic diarrhea on any 15 days during the past 30 days. prior medication: excluded: * prior foscarnet as induction or maintenance therapy. * prior u-90152. * prior ddc or d4t. * prior azt/ddi in combination or taken separately at different times. * prior non-nucleoside reverse transcriptase inhibitors (nevirapine, atevirdine, etc.). * prior protease inhibitors (although patients from actg 282 are eligible). * hiv-1 vaccine within the past 21 days. * acute treatment for a serious infection or for any opportunistic infection within the past 14 days. excluded within the past 30 days: * interferon or interleukin. * rifampin. * rifabutin. * terfenadine. * astemizole. * loratadine. * recombinant epo or g-csf. * hydroxyurea. * spv-30. * any other investigational drug. active drug or alcohol use.

Keywords: didanosine drug therapy, combination acquired immunodeficiency syndrome aids-related complex antiviral agents zidovudine