Affiliations: [a] Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| [b] Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX, USA
| [c]
Weill Cornell Medical College of Cornell University, NY, USA
Correspondence:
[*]
Correspondence to: Muralidhar L. Hegde, Department of Radiation Oncology, Houston Methodist Research Institute, Houston, Texas 77030, USA. E-mail: mlhegde@houstonmethodist.org and Anil Kumar, Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA. E-mail: kumaran@umkc.edu.
Note: [1] These authors contributed equally to the manuscript.
Abstract: With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications. On the contrary, the presence of neurological disorder frequently affects the outcome of conventional HIV-1 therapy. Although, both the children and adults suffer from the post-HIV treatment-associated cognitive impairment, adults, especially depending on the age of disease onset, are more prone to CNS dysfunction. Thus, addressing neurological complications in an HIV-1-infected patient is a delicate balance of several factors and requires characterization of the molecular signature of associated CNS disorders involving intricate cross-talk with HIV-1-derived neurotoxins and other cellular factors. In this review, we summarize some of the current data supporting both the direct and indirect mechanisms, including neuro-inflammation and genome instability in association with aging, leading to CNS dysfunction after HIV-1 infection, and discuss the potential strategies addressing the treatment or prevention of HIV-1-mediated neurotoxicity.
Keywords: AIDS, cognitive dysfunction, dementia, genome instability, human immunodeficiency virus type 1, neurodegeneration
