An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

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.

Viruses and Endogenous Retroviruses as Roots for Neuroinflammation and Neurodegenerative Diseases

“…HIV infection causes acquired immunodeficiency syndrome (AIDS) affecting multiple systems in the body. One of the complications of HIV infection is the HIV-associated neurodegenerative disorder (HAND) (Navia et al, 1986), which can develop into HIV-associated dementia (Nookala et al, 2017), the most common cause of dementia in young adults (Janssen et al, 1992) with higher prevalence among women (Duarte et al, 2020). HIV is transported to the brain with infected T-lymphocytes and monocytes (Wiley et al, 1986;Takahashi et al, 1996).…”

“…HIV is transported to the brain with infected T-lymphocytes and monocytes (Wiley et al, 1986;Takahashi et al, 1996). These long-lived cells are referred to as sources of HIV chronic infection (Nookala et al, 2017). In the brain, HIV infects primarily the immunocompetent cells, perivascular macrophages, and microglia where it replicates (Watkins et al, 1990;Albright et al, 2000).…”

“…These include HIV Tat, HIV viral protein R (Vpr), and HIV env glycoprotein gp160 cleaved product gp120. HIV viral proteins induce neuropathology by aberrant calcium signaling, mitochondrial damage, oxidative stress, excitotoxicity, and inflammation (Nookala et al, 2017), collectively leading to neuronal death (Masliah et al, 1992).…”

Humanized Mice for Infectious and Neurodegenerative disorders

“…Moreover, this study utilized female mice, whereas most MPTP studies are performed in male mice to reduce known variability observed with females. With the advent of ART for HIV-1 treatment, individuals living with HIV have longer lives with fewer co-morbidities, yet still can exhibit motor deficits like PD [176][177][178][179][180]. Thus, a major, yet recurrent question is whether HIV infection affects the development of PD-linked neurodegeneration.…”

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson’s disease

“…Although the prevalence of asymptomatic neurocognitive impairment without functional impairment may have been overestimated in the presence of too lenient neuropsychological guidelines (Gisslen, Price, & Nilsson, 2011), it has become evident over the years that there is considerable heterogeneity in pattern and severity of cognitive and motor deficits in the HIV population. Some individuals demonstrate moderate deficits in multiple domains, whereas others demonstrate little to no observable deficits (Nookala, Mitra, Chaudhari, Hegde, & Kumar, 2017). Further, a new challenge looms as individuals living with HIV infection age, with older individuals at greater risk of developing cognitive and motor deficits than are older individuals without HIV infection (Elicer, Byrd, Clark, Morgello, & Robinson‐Papp, 2018; Goodkin et al ., 2017; Sheppard, Woods, et al ., 2015; Smail & Brew, 2018).…”