The effects of high-dose recombinant soluble CD4 on human immunodeficiency virus type 1 viremia

Schacker, T.; Coombs, R.W.; Collier, A.C.; Zeh, J.E.; Fox, I.; Alam, J.; Nelson, K.; Eggert, E.; Corey, L.

Journal of Infectious Diseases 169(1): 37-40


ISSN/ISBN: 0022-1899
PMID: 8277195
DOI: 10.1093/infdis/169.1.37
Accession: 009571192

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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 mg/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 ID-90-95 of the isolate, not the ID-50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses of rsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure.