Safe use of the CXCR4 inhibitor ALX40-4C in humans

ALX40-4C is a small peptide inhibitor of the chemokine receptor CXCR4 that can inhibit X4 strains of HIV-1. Prior to the discovery of chemokine recept ors as the HIV coreceptors, ALX40-4C was used in phase I/II clinical trials to evaluate its therapeutic potential against HIV-1, making ALX40-4C the f irst anticoreceptor inhibitor to be tested in humans against HIV-1. Patient s in the highest dose groups achieved ALX40-4C levels above the effective c oncentration of the drug for nearly the entire 1-month treatment period. AL X40-4C was well tolerated by 39 of 40 asymptomatic HIV-infected patients, d espite the critical role of CXCR4 in normal development and hematopoiesis. No significant or consistent reductions in viral load were observed, but on ly 12 of the enrolled patients harbored virus types that used CXCR4. We als o found that ALX40-4C interacts with the second extracellular loop of CXCR4 and inhibits infection exclusively by blocking direct virus-CXCR4 interact ions.