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

• 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
• Journal Title: MICROORGANISMS
• Volume: Volume 10, Number 11
• Publisher: MDPI | 2022-11-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/microorganisms10112244
• Subjects: Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Microbiology; HAND; HIV neurocognitive impairment; neuroHIV; HIV; brain; adjunctive therapy; neuroinflammation; HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ACTIVE ANTIRETROVIRAL THERAPY; MAGNETIC-RESONANCE SPECTROSCOPY; CEREBROSPINAL-FLUID MARKERS; PLACEBO-CONTROLLED PHASE-3; SPATIAL WORKING-MEMORY; IN-VIVO; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE

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.