Grant: New Investigator Award - PA: HIV/AIDS Biomedical/Clinical Research

Due to similar blood and body fluid transmission routes, hepatitis B virus (HBV) is an important infection in persons living with the human immunodeficiency virus (HIV). HBV can cause serious liver disease such as cirrhosis (scarring of the liver) and liver cancer (hepatocellular carcinoma, HCC). Liver disease is the leading cause of death and hospitalizations in patients living with HIV, and therefore adequate management of hepatitis B is considered a priority in HBV/HIV coinfected patients. There is increasing evidence suggesting that molecular (genetic) characterization of the HBV, such as development of antiviral drug resistant variants, is an important factor in guiding patient management. Although both HIV and HBV can infect cells of the immune system the role of these immune cell reservoirs in HBV persistence is unknown. Our clinic cares for approximately 2800 persons with HIV and have collected sequential blood samples over 2 decades of follow-up from these patients. Approximately 15% (178/2800) patients were diagnosed with chronic HBV infection. We aim to study these persons to determine how HBV can establish a persistent infection and how this affects clinical outcome such as development of liver disease. We will analyze the genetic sequence of each virus (HIV and HBV) to determine whether coinfection can affect the development of resistance to both HBV and HIV antiviral drug therapy. Finally we will study the effect of coinfection on the host immune response to infection. This comprehensive longitudinal study of HBV and HIV coinfected patients will assess: (1) HBV and HIV genetic evolution, (2) HBV and HIV drug resistance, (3) host immune response and (4) presence of immune (ie., lymphoid) cell viral reservoirs. We aim to determine how viral interactions within dually infected immune cells impact patient clinical outcomes such as acceleration of liver disease, development of liver failure and liver-failure related death.