Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase I-II escalating dosage trial.

Study Objective: To study the safety and pharmacokinetics and to derive preliminary evidence on surrogate indicators of efficacy of recombinant soluble CD4 (rsCD4) in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex.

Design: Open label, escalating dosage, phase I-II tolerance trial.

Setting: Massachusetts General Hospital, Cedars-Sinai Medical Center, and Stanford University Medical School, three tertiary care institutions and members of the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

Instructions: Cohorts of 3 to 11 patients received rsCD4 by intravenous infusion or intramuscular injection in dosages of up to 30 mg per day for 28 days.

Measurements And Main Results: Recombinant soluble CD4 was tolerated by these patients with no significant clinical or immunologic toxicities. Serum levels of rsCD4 in patients receiving doses of 9 or 30 mg per day administered intramuscularly were in the range of rsCD4 concentrations required to inhibit replication of human immunodeficiency virus 1 (HIV-1) in vitro. A decline in serum HIV-1 p24 antigen was seen in patients receiving 30 mg of rsCD4 daily, but no such changes were noted at lower dosages.

Conclusions: Recombinant soluble CD4 is well tolerated by patients with AIDS or advanced AIDS-related complex. Our study has also provided preliminary evidence of antiviral activity of rsCD4 in vivo. Our data suggest that further trials of receptor-based therapies against HIV-1 are warranted.