Cellular and tissue sources of viral rebound primarily originate from long-lived reservoirs of HIV in individuals under antiretroviral therapy (ART). Key cellular reservoirs include CD4+ T cells, particularly memory subsets like central memory (Tcm), which harbor latent provirus. Tissue-specific sources include lymphoid tissues (lymph nodes, spleen, and gut-associated lymphoid tissue), where virus can persist despite ART. The central nervous system (CNS) acts as a sanctuary probably also due to limited drug penetration. Additionally, myeloid cells like macrophages and microglia may contribute to viral rebound. Gut tissue plays a significant role as it harbors high numbers of infected cells and provides a pro-inflammatory environment conducive to viral reactivation. In this presentation, we will explore methods used to characterize the persistent HIV reservoir across various cell subsets and tissues, highlighting their successes and limitations in identifying the viruses responsible for systemic rebound upon treatment interruption. Additionally, we will discuss how emerging technologies and multi-omics platforms can enhance our understanding of the viral reservoir and provide new insights into its dynamics and reactivation potential.
CROI Conference
