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NLM AIDSLINE

Primary HIV-1 isolates are relatively resistant to neutralization by recombinant soluble CD4 (sCD4).




 

Int Conf AIDS. 1990 Jun 20-23;6(3):117 (abstract no. S.B.88). Unique

OBJECTIVE: To determine the sensitivity of primary HIV-1 isolates to sCD4 and why patients receiving sCD4 had no consistent decrease in HIV-1 titers. METHODS: End-point-dilution cultures were used to quantify HIV-1 in plasma and peripheral blood mononuclear cells (PBMC) of patients receiving sCD4, and in untreated patient plasma inoculated with sCD4. Neutralization by sCD4 was performed on HTLV-IIIB, HTLV-IIIRF, LAV-2(ROD), and primary HIV-1 (P1) isolates from 10 patients with various stages of disease. RESULTS: No consistent decrease in HIV-1 titers in plasma or PBMC was observed in patients on sCD4 (30 mg/d). Ex vivo experiments showed that up to 1 mg/ml of sCD4 had a minimal effect on plasma HIV-1 titer. In standard neutralization assays, 10 primary HIV-1 isolates were relatively refractory to several sCD4 constructs with 90% inhibitory doses (ID(90)) ranging from 200-2700x that of HTLV-IIIB. These observations were made using two different monomeric sCD4 preparations and two multimeric CD4-Ig hybrid molecules (CD4-IgG; CD4-IgM). The ID(90) of one primary virus decreased from 160 ug to 1.5 ug after being cultured in H9 cells for 1 year. Despite the refractoriness to sCD4, infection of primary HIV-1 isolates were easily neutralized by an anti-CD4 monoclonal antibody (Leu3A). CONCLUSION: In contrast to laboratory strains of HIV-1, high concentrations of sCD4 are required to neutralize primary isolates. This poses a formidable problem for CD4-based therapeutics. The refractoriness of sCD4 neutralization is, we believe, due to low affinities between CD4 and gp120's of primary HIV-1 isolates.

Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Antigens, CD4/*IMMUNOLOGY Cells, Cultured Human HIV Envelope Protein gp120/IMMUNOLOGY HIV-1/*IMMUNOLOGY Neutralization Tests Recombinant Proteins/IMMUNOLOGY Solubility ABSTRACT



 




Information in this article was accurate in December 30, 1990. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.