Mapping the anatomical distribution and persistence of HIV-infected cell clones in tissues: implications for HIV cure strategies.

Purpose of review: This review summarizes recent literature about current approaches to track HIV-infected T cell clones, their anatomical distribution and phenotypic features under antiretroviral therapy (ART) suppression, as well as the implications of clonal expansion for HIV cure strategies.

Recent findings: Multiple studies have shown that clones of infected cells are shared between anatomical sites, highlighting their trafficking throughout the body. Newly generated data further confirm a lack of HIV compartmentalization between anatomical sites, suggesting the absence of viral replication in blood and tissues under ART despite previous reports of low antiretroviral penetration in certain tissues. Recent observations also suggest that infected cells belonging to the same clone may display different phenotypes depending on their anatomical location, although direct proof of the plasticity of infected T cell clones is still lacking.

Summary: Postmortem studies have identified HIV-infected cells in almost all tissues analyzed, highlighting the importance of studying tissues to gain further insights into HIV persistence and clonality. Sensitive approaches that enable simultaneous analysis of the T-cell receptor and phenotypic traits of HIV-infected clones from matched blood and tissue samples will be key to unravel antigen specificity, as well as the distribution of infected clones across anatomical compartments and their phenotypic plasticity, ultimately facilitating the development of therapeutic strategies.