Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study

Study Objective: To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. Design: A partially randomized phase I and II outpatient, dose-ranging study. Setting: Four university medical centers involving government-supported referral AIDS Clinical Trial Units. Patients: Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers. Interventions: Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit. Measurements and Main Results: In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P < 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in atients receiving 0.005 mg/kg. Conclusions: Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.