a multi-center, open-label, ascending, multiple oral dose, safety, tolerance and pharmacokinetic study of 3'-deoxy-3'-fluorothymidine (flt) in patients with acquired immune deficiency syndrome (aids) or aids-related complex (arc)

Conditions: HIV Infections

Summary: to assess the tolerance and toxicity profile of deoxy-3'-fluorothymidine (flt) after multiple oral dosing for 16 weeks. to characterize the steady-state pharmacokinetics of flt after multiple oral doses. to assess the effect of flt on immunologic and virologic markers of hiv infection (cd4+ lymphocyte count, p24 antigen, viremia) in patients with aids or aids related complex (arc) after multiple oral dosing for 16 weeks.


Eligibility criteria:
inclusion criteria concurrent medication: allowed: * aerosolized pentamidine for pneumocystis carinii pneumonia (pcp) prophylaxis. * up to 14 days of systemic therapy for minor opportunistic infections such as candidiasis, mucocutaneous herpes simplex or cutaneous herpes zoster infections. patients must have the following: * aids or aids related complex (arc) as defined by the cdc. * positive antibody to hiv as determined by a commercially licensed elisa test kit, confirmed by western blot analysis. exclusion criteria co-existing condition: patients with the following conditions or symptoms are excluded: * symptomatic visceral kaposi's sarcoma or progression of kaposi's sarcoma within the month prior to study entry (progression is defined as more than a 25 percent increase in the product of bidirectional measurement of indicator lesions and/or more than a 25 percent increase in the number of new lesions). * concurrent neoplasms other than kaposi's sarcoma or basal cell carcinoma of the skin. patients who have had a malignancy in the past that has been in complete remission for 1 year without therapy may be enrolled. * signs or symptoms of neuropathy and a vibratron 2 score = or \> 4 for either great toe. concurrent medication: excluded: * acute therapy for aids-related infection. * systemic maintenance therapy for aids-defining opportunistic infection. * recombinant erythropoietin. * long term therapy with either aspirin or probenecid. concurrent treatment: excluded: * blood transfusion more than once per month. patients with the following are excluded: * symptomatic visceral kaposi's sarcoma or progression of kaposi's sarcoma within the month prior to study entry. * unwilling to sign an informed consent or patients unwilling to be followed at the medical center where they were enrolled for the duration of the study and follow-up as required. * history of intolerance to zidovudine (azt) at any dose as demonstrated by an azt related decrease in hemoglobin levels of at least 2 g/dl or azt related depression of neutrophils of at least 200 cells/mm3 to \< 750 cells/mm3 which required discontinuation of azt therapy. * diseases or conditions listed in exclusion co-existing conditions. prior medication: excluded: * antiretroviral agents within 14 days of study entry. * immunomodulating agents or corticosteroids within 30 days prior to study entry. * treatment for acute pneumocystis carinii pneumonia within 2 weeks prior to study entry. prior treatment: excluded: * blood transfusions within 7 days prior to study entry. * radiation therapy for kaposi's sarcoma within 30 days prior to study entry. active substance abuse.

Keywords: acquired immunodeficiency syndrome