Viremic non-progression in HIV/SIV infection: A tied game between virus and host

High-efficacy antiretroviral treatment (ART) has been a game-changer for HIV/AIDS pandemic, but incomplete CD4⁺ T cell recovery and persistent chronic immune activation still affect HIV-suppressed people. Exceptional cases of HIV infection that naturally exhibit delayed disease progression provide invaluable insights into protective biological mechanisms with potential clinical application. Viremic non-progressors (VNPs) represent an extremely rare population of individuals with HIV, characterized by preservation of the CD4⁺ T cell compartment despite persistent high levels of viral load (>10,000 copies/mL). While only a few studies have investigated the immunovirological characteristics of adult and pediatric VNPs, most of our knowledge about this phenotype stems from its non-human-primate counterpart, the natural simian immunodeficiency virus (SIV) hosts. In this review, we synthesize the insights gained from recent studies of natural SIV hosts and VNPs and evaluate the potential similarities and differences in the mechanisms that underlie the absence of pathogenesis, with special focus on the control of immune activation.