Sydney Corey1, Bryan R Smith2, Irene C M Cortese3. 1. Experimental Immunotherapeutics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, 5C103, Bethesda, MD, 20892-1684, USA. 2. Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. 3. Experimental Immunotherapeutics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, 5C103, Bethesda, MD, 20892-1684, USA. corteseir@ninds.nih.gov.
Abstract
PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection that remains an important cause of morbidity and mortality in people living with HIV (PLWH). Immune checkpoint molecules are negative regulators of the immune response that have been targeted as a strategy to bolster anti-viral immunity in PML, with varied outcomes reported. While initiation and optimization of antiretroviral therapy remains the standard of care in HIV-related PML, the specific opportunities and risks for checkpoint blockade in these cases should be explored. RECENT FINDINGS: As of April 15, 2022, only 5 of the 53 total published cases of PML treated with checkpoint blockade had underlying HIV infection; four of these had a favorable outcome. The risk of promoting immune reconstitution inflammatory syndrome is a major concern and underscores the importance of patient selection and monitoring. Checkpoint blockade warrants further exploration as a potentially promising option for treatment escalation in HIV-related PML.
PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection that remains an important cause of morbidity and mortality in people living with HIV (PLWH). Immune checkpoint molecules are negative regulators of the immune response that have been targeted as a strategy to bolster anti-viral immunity in PML, with varied outcomes reported. While initiation and optimization of antiretroviral therapy remains the standard of care in HIV-related PML, the specific opportunities and risks for checkpoint blockade in these cases should be explored. RECENT FINDINGS: As of April 15, 2022, only 5 of the 53 total published cases of PML treated with checkpoint blockade had underlying HIV infection; four of these had a favorable outcome. The risk of promoting immune reconstitution inflammatory syndrome is a major concern and underscores the importance of patient selection and monitoring. Checkpoint blockade warrants further exploration as a potentially promising option for treatment escalation in HIV-related PML.
Authors: Andrea Antinori; Antonella Cingolani; Patrizia Lorenzini; Maria Letizia Giancola; Ilaria Uccella; Simona Bossolasco; Susanna Grisetti; Francesca Moretti; Beniamino Vigo; Marco Bongiovanni; Bruno Del Grosso; Maria Irene Arcidiacono; Giovanni Carlo Fibbia; Maurizio Mena; Maria Grazia Finazzi; Giovanni Guaraldi; Adriana Ammassari; Antonella d'Arminio Monforte; Paola Cinque; Andrea De Luca Journal: J Neurovirol Date: 2003 Impact factor: 2.643