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

      Nature medicine

      physiology, Virus Replication, immunology, Virus Latency, Viral Load, T-Lymphocytes, Molecular Sequence Data, Immunologic Memory, Humans, Homeostasis, HIV-1, virology, drug therapy, HIV Infections, Cell Survival, Cell Proliferation, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active, therapeutic use, Anti-HIV Agents

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          Abstract

          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 (T(CM)) and transitional memory (T(TM)) 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 T(CM) 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 T(TM) 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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          Author and article information

          Journal
          10.1038/nm.1972
          2859814
          19543283

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