Infectious disease

Mouse studies identified a prodrug of the HIV integrase inhibitor Tivicay dolutegravir that could help treat HIV infection. The prodrug consists of Tivicay modified with myristic acid for formation of hydrophobic and lipophilic nanocrystals that extend the half-life of the active drug substance. In mice, the active drug substance of the prodrug had a greater area under the curve (AUC) for blood concentration-time than free Tivicay. In a humanized mouse model of HIV infection, the prodrug decreased viral titers in the plasma and HIV p24 levels in the spleen. In another humanized mouse model of HIV infection, the prodrug decreased levels of the HIV RNA genome in the spleen and lymph nodes. Next steps could include optimizing the prodrug formulation for use in patients...