trial of an alternative dosing regimen of oral retrovir in patients with aids or advanced arc

Conditions: HIV Infections

Summary: to evaluate the safety and tolerance, in patients with severe clinical manifestations of hiv infection, of zidovudine (azt) administered daily for 48 weeks as a low dose every 4 hours or a higher dose every 12 hours.


Eligibility criteria:
inclusion criteria concurrent medication: allowed: - prophylaxis or treatment for pneumocystis carinii pneumonia (pcp) consisting of either trimethoprim / sulfamethoxazole, aerosolized pentamidine, pyrimethamine / sulfadoxine, or dapsone allowed at the discretion of the investigator. patients with the following are excluded: * any immediately life-threatening infection or medical condition present at the time of study entry. * any active opportunistic or other infection requiring chronic therapy at the time of study entry. patients with pcp may be randomized to study medication following a minimum 7-day course of therapy resulting in stabilization of their disease. patients with stabilized disease must have a fever \ 60 mm, and an arterial/alveolar gradient = or \< 30 mm. * diagnosis of aids dementia complex. * received more than 4 weeks of antiretroviral therapy or who previously discontinued antiretroviral therapy due to drug related toxicity. * diseases and conditions listed in exclusion co-existing conditions. patients must have the following: * seropositive for hiv infection documented by any federally licensed elisa and confirmed by western blot. * advanced hiv disease or aids-related complex. * ability to give informed consent. exclusion criteria co-existing condition: patients with the following conditions or symptoms are excluded: * aids with malignant disease likely to require cytotoxic chemotherapy. * diagnosis of aids dementia complex. * impaired renal function ( creatinine clearance \ 2 mg/dl). * impaired hepatic function ( alt = or \> 5 x upper limit of normal). * fever \> 39 c at entry. concurrent medication: excluded: * any other experimental therapy. * drugs which cause significant bone marrow suppression. * cytolytic chemotherapy. * drugs which cause significant nephrotoxicity or hepatotoxicity. concurrent treatment: excluded: * radiation therapy (with the exception of electron beam therapy to an area \< 100 cm2). prior medication: excluded within 2 weeks of study entry: - any other experimental therapy. drugs which cause significant bone marrow suppression. cytolytic chemotherapy. drugs which cause significant nephrotoxicity or hepatotoxicity. excluded within 4 weeks of entry: - immunomodulating agents, including pharmacological doses of steroids for more than 10 days (except for management of severe pcp in which case duration should not exceed 21 days). interferon. isoprinosine. il-2. excluded within 8 weeks of entry: - antiretroviral agents including: - ribavirin. dideoxycytidine (ddc). dideoxyadenosine (dda). didanosine (ddi). foscarnet. dextran sulfate. al-721. retrovir (zidovudine, azt) for greater than 4 weeks or within 90 days of study entry, or patients who originally discontinued retrovir due to drug-related toxicity. drugs metabolized by hepatic glucuronidation may alter the metabolism of retrovir and should not be used chronically. prior treatment: excluded: * radiation therapy (with the exception of electron beam therapy to an area \< 100 cm2) within 2 weeks of study entry. known active drug or alcohol abuse.

Keywords: acquired immunodeficiency syndrome aids-related complex zidovudine