In vitro inhibition of HIV-1 by Met-SDF-1 beta alone or in combination with antiretroviral drugs

Compounds that can block the CXCR4 chemokine receptor are a promising new c lass of antiretroviral agents. In these experiments we studied the effect o f a modified form of the native stromal cell-derived factor-1 (SDF-1), Met- SDF-1 beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentra tions (IC50) were derived from six separate experiments. The IC50 against t he two HIV-1 isolates was in 1.0-2.8 mug/ml range for Met-SDF-1 beta. Met-S DF-1 beta showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1 beta was combin ed with efavirenz. No cellular toxicity was observed at the highest concent rations when these agents were used either singly or in combination. This c ompound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretrovira l drug therapies.