CONTINUOUS PRESENCE OF CD4-PE40 IS REQUIRED FOR ANTIVIRAL ACTIVITY AGAINST SINGLE-PASSAGE HIV ISOLATES AND INFECTED PERIPHERAL-BLOOD MONONUCLEAR-CELLS

CD4-PE40, a recombinant protein consisting of a portion of human CD4 l inked to Pseudomonas aeruginosa exotoxin, was studied in vitro to asse ss its ability to inhibit the replication of primary isolates of HIV. CD4-PE40 was added to cultures of phytohemagglutin (PHA)-stimulated no rmal peripheral blood mononuclear cells (PBMCs) infected either with t he laboratory strain HIVIIIb or single-passage virus stocks derived fr om patient PBMCs. Results showed that the replication of HIVIIIb was i nhibited by a single pulse of CD4-PE40 and, more significantly, by con tinuous exposure to the drug. The replication of primary virus isolate s, however, was inhibited only by continuous exposure to CD4-PE40. cul tures of freshly isolated PBMCs from HIV-seropositive individuals that were directly treated with CD4-PE40 before culture also required the continuous presence of drug to demonstrate inhibition of HIV replicati on. These results suggest that continuous administration of CD4-PE40 m ay be required to produce a significant anti-HIV effect in vivo.