HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

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Abstract
Highly active antiretroviral therapy is unable to eliminate HIV infection, because the virus persists in latently infected CD4+ T cells—a so-called virus reservoir. Rafick-Pierre Sekaly and his colleagues have shown that central memory CD4+ T cells and transitional memory CD4+ T cells are the main cellular reservoirs for HIV, and they suggest a mechanism that ensures the stability of this reservoir of virus. HIV persists in a reservoir of latently infected CD4+ T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (TCM) and transitional memory (TTM) CD4+ T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in TCM cells in subjects showing reconstitution of the CD4+ compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in TTM cells from aviremic individuals with low CD4+ counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

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