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

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; Frank Maldarelli; Irini Sereti

doi:10.1038/s41591-023-02387-4

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

Nat Med. 2023 Jun;29(6):1364-1369. doi: 10.1038/s41591-023-02387-4. Epub 2023 Jun 15.

Authors

Andrea Lisco^#¹, Camille Lange^#^{2

3}, Maura Manion¹, Safia Kuriakose⁴, Robin Dewar⁵, Robert J Gorelick⁶, Kristi Huik⁷, Quan Yu⁸, Dima A Hammoud⁹, Bryan R Smith¹⁰, Pawel Muranski⁸, Catherine Rehm¹, Brad T Sherman¹¹, Craig Sykes¹², Natalie Lindo⁷, Peiying Ye¹, Katherine M Bricker¹, Brandon F Keele⁶, Christine M Fennessey⁶, Frank Maldarelli^#¹³, Irini Sereti^#¹⁴

Affiliations

¹ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
² Clinical Retrovirology Section, HIV Dynamics and Replication Program National Cancer Institute, National Institutes of Health, Frederick, MD, USA. clange@hivresearch.org.
³ Military HIV Research Program, Walter Reed Army Institute of Research, Henry M. Jackson Foundation for the Advancement of Military Medicine, Silver Spring, MD, USA. clange@hivresearch.org.
⁴ Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Bethesda, MD, USA.
⁵ Virus Isolation and Serology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁶ AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
⁷ Clinical Retrovirology Section, HIV Dynamics and Replication Program National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
⁸ Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁹ Center for Infectious Disease Imaging, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹¹ Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
¹² Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹³ Clinical Retrovirology Section, HIV Dynamics and Replication Program National Cancer Institute, National Institutes of Health, Frederick, MD, USA. fmalli@mail.nih.gov.
¹⁴ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. isereti@niaid.nih.gov.

^# Contributed equally.

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.

Publication types

Case Reports

MeSH terms

Brain
Central Nervous System
HIV Infections*
Humans
Immune Reconstitution Inflammatory Syndrome* / drug therapy
Immune Reconstitution Inflammatory Syndrome* / etiology
Leukoencephalopathy, Progressive Multifocal* / drug therapy
Leukoencephalopathy, Progressive Multifocal* / etiology
Male
Middle Aged

Abstract

Publication types

MeSH terms

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