a randomized study of activity, safety, and tolerance of oral ro 24-7429 (tat antagonist) in patients with hiv infection

Conditions: HIV Infections

Summary: to study the anti-hiv activity of the various doses of ro 24-7429 monotherapy based on virologic and immunologic endpoints. to study the safety and tolerance of ro 24-7429. to explore relationships between exposure to ro 24-7429 and its metabolites and antiviral activity and drug toxicity. to determine a safe, tolerable, and active dose regimen of ro 24-7429, and to make preliminary observations of ro 24-7429 in combination with another antiretroviral nucleoside. the hiv genome contains a number of genes that regulate viral replication. control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. the tat (transactivator of transcription of hiv) antagonist ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of hiv infection.

the hiv genome contains a number of genes that regulate viral replication. control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. the tat (transactivator of transcription of hiv) antagonist ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of hiv infection. ninety-six patients (four treatment arms of 24 patients each) are randomized to receive oral ro 24-7429 at 1 of 3 doses or nucleoside control (either zidovudine or didanosine). the study will be blinded only for the arms receiving ro 24-7429. treatment continues for 12 weeks. after 12 weeks, patients on the nucleoside control arm receive the highest tolerated dose of ro 24-7429 in addition to their nucleoside.

Eligibility criteria:
inclusion criteria concurrent medication: allowed: * chemoprophylaxis for p. carinii pneumonia, tb, and mucocutaneous candidiasis. * methadone maintenance. * hormonal contraceptives. patients must have: * hiv-1 seropositivity. * cd4 count 50 - 500 cells/mm3. * life expectancy of at least 24 weeks. * stable weight (+/- 2 kg) by 28 days prior to study entry (by history). note: * at least 50 percent of patients must be p24 antigen positive (\>= 50 pg/ml). exclusion criteria co-existing condition: patients with the following symptoms and conditions are excluded: * known or suspected hypersensitivity to benzodiazepines. * presence of any malignancy other than basal cell carcinoma or limited cutaneous kaposi's sarcoma (defined as no more than five lesions with no mucosal involvement). * ongoing diarrhea, defined as more than 2 liquid stools per day. * history, physical exam, or laboratory results consistent with a subclinical aids-defining opportunistic infection. * grade 2 or greater signs and symptoms of aids dementia complex. * evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, dermatologic, or allergic disease. concurrent medication: excluded: * chronic suppressive therapy for cmv, mai, toxoplasmosis, cryptococcosis, cryptosporidiosis, coccidioidomycosis, and histoplasmosis. * ddc, ddi, azt (except for control groups) or other experimental antiretrovirals or immunomodulating agents. * other medications excluded from the study. patients with the following prior conditions are excluded: * history of serious adverse reactions to benzodiazepines. * history of intolerance to azt at 600 mg/day or less or ddi at 400 mg/day or less. * history of unexplained fever, defined as a temperature of 38.5 deg c or greater with or without night sweats for more than 7 of the past 28 days. prior medication: excluded: * benzodiazepines within 14 days prior to study entry. active drug or alcohol abuse that would interfere with study compliance.

Keywords: didanosine acquired immunodeficiency syndrome aids-related complex antiviral agents zidovudine gene products, tat