Grant: Fellowship - Priority Announcement - HIV/AIDS and/or STBBI

Hepatitis C is a curable disease, but remains a public health problem. Hepatitis C, caused by the hepatitis C virus (HCV), is transmitted by infected blood and mainly affects the liver. Most people infected with HCV develop a lifelong disease, while around 30% can clear the infection spontaneously. If left undiagnosed, hepatitis C can lead to liver cancer, the fourth leading cause of cancer deaths. We know that the body's defenses in people with persistent hepatitis C are dysfunctional and unable to kill the virus. Antiviral treatment can effectively eliminate the virus and partially restore these defenses. However, it is not known whether the restored defenses protect against further encounters with the virus. Certain groups, such as people who inject drugs, are more exposed to the risk of infection by this virus. What's more, there is currently no vaccine capable of preventing (re)infection with the hepatitis C virus. The aim of this project is to determine whether the body's defenses against HCV in this vulnerable population can be rewired after recovery and be functional in the event of reinfection. The study of people who inject drugs that are reinfected with HCV after cure represents a real-life simulation of vaccination. First, we plan to determine whether early initiation of treatment induces better recovery of the body's defenses. To do this, we will analyze the white blood cells and plasma, which are responsible for defending against infection, of treated individuals. We will then study the dynamics and characteristics of these cells during reinfection after recovery, and compare them with those of people who can eliminate HCV spontaneously, the gold standard of protection. We hope that these results will inform decision-makers as to the timing of therapy initiation in the recovery of HCV defenses. The characteristics of the cells defined by this study will serve as a reference for vaccine development, given their state of recovery after cure.