BioCentury
ARTICLE | Distillery Therapeutics

Infectious disease

January 11, 2017 12:50 AM UTC

Mouse studies suggest inhibiting IFNAR2 or IFNAR1 could help treat HIV1 infection. In a humanized mouse model of chronic HIV infection, an anti-IFNAR2 mAb decreased plasma viral load and levels of exhaustion markers such as PD-1 on circulating CD8+ T cells compared with a control mAb. Also in the model, the anti-IFNAR2 mAb plus a cocktail of the antiretrovirals (ARVs) Isentress raltegravir, emtricitabine and tenofovir decreased plasma and latent splenic viral loads compared with the cocktail plus a control mAb. In the same model, an anti-IFNAR1 mAb plus the ARV cocktail decreased levels of splenic T cell exhaustion markers such as PD-1. Also in the model, the anti-IFNAR1 mAb plus the ARV cocktail decreased latent viral loads in the spleen and bone marrow compared with either the mAb or cocktail alone, and upon cessation of ARV therapy, the mAb increased the time to plasma viremia rebound compared with a control mAb. Next steps include identifying regulators of T cell exhaustion downstream of IFNAR2 and IFNAR1 that could promote antiviral T cell activity without inhibiting the receptors’ antiviral functions (see “Give Me a Break”).

Merck & Co. Inc. markets Isentress, an HIV integrase inhibitor, to treat HIV infection...