HGS101 is a fully humanized CCR5 monoclonal antibody that exhibits high affinity for CCR5. It binds to the second extracellular loop (ECL-2) and functions as a signaling antagonist. HGS101 restores the inhibitory effect of Maraviroc in Maraviroc-resistant HIV-1 infected PBMCs. In an uninfected simian immunodeficiency virus model of rhesus monkeys, HGS101 shows anti-HIV activity by inhibiting CCR5 signaling.

HGS101 (1 h) demonstrates EC50 values for maraviroc-sensitive, maraviroc-resistant, and maraviroc-tolerant HIV-1 strains in JC6 cells at 0.001 μg/mL, 0.0003 μg/mL, and 0.00002 μg/mL, respectively, under the presence of Maraviroc. In PBMCs, HGS101 under the same conditions results in EC50 values of 0.03 μg/mL, 0.03 μg/mL, and 0.01 μg/mL for the respective HIV-1 strains. Moreover, HGS101 at 0.3 µg/mL for 1 h can restore the inhibitory effect of Maraviroc in PBMCs against maraviroc-resistant HIV-1, reducing the EC50 of Maraviroc to 0.007 nM.

HGS101 (10 mg/kg, intravenous injection every 15 days for a total of 10 doses) exhibits anti-HIV activity in a rhesus macaque model not infected with simian immunodeficiency virus by inhibiting the CCR5 signaling pathway.