Relative resistance of primary HIV-1 isolates to neutralization by soluble CD4

Replication of the human immunodeficiency virus type 1 (HIV-1) underlies the pathogenesis and progression of the acquired immunodeficiency syndrome (AIDS). A soluble form of the virus receptor, CD4, has been developed as a potential therapeutic agent with good activity against laboratory strains of HIV-1 in vitro. However, quantitative virologic studies performed to date on the blood of patients receiving recombinant soluble CD4 (sCD4) demonstrated no efficacy in vivo despite good drug levels in serum. These results led us to examine the neutralizing activity of sCD4 against multiple primary HIV-1 isolates from infected patients. The findings demonstrate that primary isolates were significantly more resistant to sCD4 than were laboratory strains, which suggests a need to reevaluate CD4-based therapies and to conduct better designed preclinical studies that include experiments performed on patient viral isolates.