Immune reconstitution inflammatory syndrome drives emergence of HIV drug resistance from multiple anatomic compartments in a person living with HIV

免疫重建炎症综合征导致 HIV 感染者体内多个解剖部位出现 HIV 耐药性

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作者:Andrea Lisco #, Camille Lange #, Maura Manion, Safia Kuriakose, Robin Dewar, Robert J Gorelick, Kristi Huik, Quan Yu, Dima A Hammoud, Bryan R Smith, Pawel Muranski, Catherine Rehm, Brad T Sherman, Craig Sykes, Natalie Lindo, Peiying Ye, Katherine M Bricker, Brandon F Keele, Christine M Fennessey, Fr

Abstract

Reservoirs of HIV maintained in anatomic compartments during antiretroviral therapy prevent HIV eradication. However, mechanisms driving their persistence and interventions to control them remain elusive. Here we report the presence of an inducible HIV reservoir within antigen-specific CD4+T cells in the central nervous system of a 59-year-old male with progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS). HIV production during PML-IRIS was suppressed by modulating inflammation with corticosteroids; selection of HIV drug resistance caused subsequent breakthrough viremia. Therefore, inflammation can influence the composition, distribution and induction of HIV reservoirs, warranting it as a key consideration for developing effective HIV remission strategies.

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