A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment

• Type of Material: Article
• Authors: Aaron Scanlan, Atlanta Veterans Affairs Medical Center; Zhan Zhang, Atlanta Veterans Affairs Medical Center; Rajeth Koneru, Atlanta Veterans Affairs Medical Center; Monica Reece, Emory University; Christina Gavegnano, Emory University; Albert Anderson, Emory University; William Tyor, Emory University
• Language: English
• Date: 2022-11-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/microorganisms10112244
• Title of Journal or Parent Work: MICROORGANISMS
• Volume: 10
• Issue: 11
• Grant/Funding Information: M.R. and C.G. are supported through R01 MH116695-5. Z.Z. is supported by VA Merit award BX005402-01. R.K. is supported by VA Merit Award BX001506-3 and VA Merit award BX005402-01.; A.S. is supported through R01 NS115650-01. W.T. is supported through VA Merit Award BX001506-3 and R01 MH116695-5.
• Keywords: Microbiology; adjunctive therapy; brain; Life Sciences & Biomedicine; ACTIVE ANTIRETROVIRAL THERAPY; ALZHEIMERS-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; neuroHIV; COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED PHASE-3; IN-VIVO; HAND; HIV; HIV neurocognitive impairment; Science & Technology; SPATIAL WORKING-MEMORY; CENTRAL-NERVOUS-SYSTEM; neuroinflammation; CEREBROSPINAL-FLUID MARKERS; MAGNETIC-RESONANCE SPECTROSCOPY
• Research Categories: Health Sciences, Pathology

Abstract

Neurocognitive impairment (NCI) associated with HIV infection of the brain impacts a large proportion of people with HIV (PWH) regardless of antiretroviral therapy (ART). While the number of PWH and severe NCI has dropped considerably with the introduction of ART, the sole use of ART is not sufficient to prevent or arrest NCI in many PWH. As the HIV field continues to investigate cure strategies, adjunctive therapies are greatly needed. HIV imaging, cerebrospinal fluid, and pathological studies point to the presence of continual inflammation, and the presence of HIV RNA, DNA, and proteins in the brain despite ART. Clinical trials exploring potential adjunctive therapeutics for the treatment of HIV NCI over the last few decades have had limited success. Ideally, future research and development of novel compounds need to address both the HIV replication and neuroinflammation associated with HIV infection in the brain. Brain mononuclear phagocytes (MPs) are the primary instigators of inflammation and HIV protein expression; therefore, adjunctive treatments that act on MPs, such as immunomodulating agents, look promising. In this review, we will highlight recent developments of innovative therapies and discuss future approaches for HIV NCI treatment.