Recent advances in the discovery and development of TLR ligands as novel therapeutics for chronic HBV and HIV infections.

INTRODUCTION: Toll-like receptor (TLR) ligands remain as promising antiviral drug candidates for the treatment of chronic viral infections. Basic research on the mechanisms of antiviral activity of TLR ligands in preclinical animal models and clinical testing of drug candidates have been carried out in recent years. Areas covered: This review provides an overview of the preclinical and clinical testing of TLR ligands in two major viral infections: hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Recent results have further demonstrated the potent antiviral activity of various TLR ligands . A TLR7 agonist is in clinical trials for the treatment of chronic HBV infection while a HBV vaccine using a TLR9 ligand as an adjuvant has proven to be superior to conventional HBV vaccines and has been approved for clinical use. Generally, TLR activation may achieve viral control mainly by promoting adaptive immunity to viral proteins. Expert opinion: Recent research in this field indicates that TLR ligands could be developed as clinically effective drugs if the obstacles concerning toxicity and application routes are overcome. TLR-mediated promotion of adaptive immunity is a major issue for future studies and will determine the future development of TLR ligands as drugs for immunomodulation.