Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

Version 1 : Received: 3 November 2023 / Approved: 6 November 2023 / Online: 6 November 2023 (11:31:26 CET)

A peer-reviewed article of this Preprint also exists.

Mohammadzadeh, N.; Chomont, N.; Estaquier, J.; Cohen, E.A.; Power, C. Is the Central Nervous System Reservoir a Hurdle for an HIV Cure? Viruses 2023, 15, 2385. Mohammadzadeh, N.; Chomont, N.; Estaquier, J.; Cohen, E.A.; Power, C. Is the Central Nervous System Reservoir a Hurdle for an HIV Cure? Viruses 2023, 15, 2385.

Abstract

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and increases life expectancy. Despite these substantial advances, ART is a lifelong treatment for people with HIV (PWH) and upon cessation or interruption, the virus quickly rebounds in plasma and anatomic sites including the central nervous system (CNS), resulting in disease progression. With recent advances in quantifying viral burden, detection of genetically intact viral genomes, and isolation of replication-competent virus from brain tissues of PWH receiving ART, it has become apparent that the CNS viral reservoir (largely comprised of macrophage type cells) poses a substantial challenge for HIV cure strategies. Other obstacles impacting the cure of HIV include ageing populations, substance use, comorbidities, limited antiretroviral drug efficacy in CNS cells and ART-associated neurotoxicity. Herein, we review recent findings including studies of the proviral integration sites, reservoir decay rates, and new treatment/prevention strategies in the context of the CNS, together with highlighting the next steps for investigations of the CNS as a viral reservoir.

Keywords

HIV; anatomical reservoirs; nervous system; persistence; cure strategies

Subject

Biology and Life Sciences, Immunology and Microbiology

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