In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1) isolates require up to 1000 times greater serum levels of recombinant soluble CD4 (rsCD4) than have ever been given. To determine if sufficient serum levels of rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were given single-dose boluses of 2, 4, 6, 8, and 10 rug/kg intravenous rsCD4. Plasma HIV-1 cultures were done after infusion. Three subjects demonstrated a dose-dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on plasma HIV-1 viremia was associated with the in vitro ID90-95 of the isolate, not the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses ofrsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure.
Bibliographical noteFunding Information:
Received 2 June 1993; revised 9 August 1993. Presented in part: Fifth International Conference on Antiviral Research. Vancouver. Canada, March 1992; American Federation for Clinical Research national meeting. Baltimore. May 1992. Informed consent was obtained from each patient. and human experimentation guidelines of the Human Subjects Review Committee ofthe University of Washington were followed. Grant support: National Institutes of Health (AI-67664, AI-27757. AI-07044. and RR-00037). Reprints or correspondence: Dr. Lawrence Corey. Pacific Medical Center. Room 9307.1200 12th Ave. S.. Seattle. WA 98144.