Francesco R. Simonetti
My research focuses on the persistence of HIV infection and its interplay with our immune system. The development of antiretroviral drugs changed the face of the HIV pandemic, transforming a devastating disease into a manageable chronic condition. However, despite successful treatment, HIV persists, integrated into the genome of infected cells as part of what we call the latent reservoir. Because of this reservoir, therapy must be continued indefinitely, requiring public health systems to deliver medications to all 38 million people living with HIV for life. Thus, understanding the mechanisms of HIV reservoir maintenance is paramount for the development of novel curative strategies.
Previous studies showed that the proliferation of infected CD4+ T cells is a major cause of HIV persistence. In the laboratory of Robert and Janet Siliciano, I tried to untangle which forces drive HIV-infected clones to expand over time and survive. My thesis work demonstrated that immune responses to chronic antigens, such as those from other common viral infections, play a major role in determining the fate of infected cells. In other words, the T cells’ “day job” drives reservoir persistence. In most cases, the HIV provirus is just a passenger. Our work shows that HIV leaves a deep footprint on the immune system, which imposes huge challenges for future therapeutic interventions.