Department of Microbiology & Immunology Seminar: “Residual Viremia on Antiretroviral Therapy: From the Tip of the Iceberg to the Depths of HIV-1 Persistence”
Speaker: Dr. Francesco R. Simonetti
Assistant Professor, Division of Infectious Diseases, Johns Hopkins University, School of Medicine, Baltimore, MD
Title: “Residual Viremia on Antiretroviral Therapy: From the Tip of the Iceberg to the Depths of HIV-1 Persistence”
HIV replication can be suppressed with antiretroviral therapy (ART), but individuals who stop taking ART soon become viremic again due to the presence of a latent HIV reservoir. Some people experience extended times of detectable viremia despite optimal adherence to ART. The Simonetti Lab investigates the source of nonsuppressible viremia (NSV) in treatment-adherent patients to provide a better understanding HIV reservoir biology and virus-host interactions. This seminar will discuss recent work in which his team identified clonally expanded T cells harboring HIV proviruses with small deletions or mutations in the 5′-leader, the UTR that includes the major splice donor site of viral RNA. These studies improve our understanding of NSV and the regulation of viral functions in the 5′-leader with implications for rationalized care in individuals with NSV. Ongoing research in the lab also focused on the mechanisms driving constant virus production from only few, specific, infected clones, based on the hypothesis that frequent stimulation from chronic antigens, including self-antigens, leads to the spontaneous activation of infected T cells and reservoir transcriptional activity.