Abstract
Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.
Highlights
Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, neurocognitive impairments (NCI) and affective alterations have been associated with the disease [1,2]
The identification of human immunodeficiency virus type 1 (HIV-1) as the retroviral etiology of AIDS [4,5] led to the hypothesis that NCI and affective alterations may result from the direct effect of the virus on the brain
HIV-1 penetrates the central nervous system (CNS) early in the course of infection [6], evidenced by the presence of HIV-1 in postmortem brain tissue [7,8,9], findings which led to the characterization of this progressive dementia, which became known as AIDS dementia complex (ADC, recognized as HIV-associated dementia (HAD))
Summary
Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, neurocognitive impairments (NCI) and affective alterations have been associated with the disease [1,2]. In the AIDS epidemic, underlying focal processes and opportunistic infections accounted for approximately 30% of the neurological complications in individuals with AIDS; a progressive dementia, was more commonly reported [3]. HIV-1 penetrates the central nervous system (CNS) early in the course of infection [6], evidenced by the presence of HIV-1 in postmortem brain tissue [7,8,9], findings which led to the characterization of this progressive dementia, which became known as AIDS dementia complex (ADC, recognized as HIV-associated dementia (HAD)). ADC, which afflicted approximately 66% of autopsy-verified AIDS patients early in the epidemic, was a neurological syndrome primarily occurring during the later phases of systemic AIDS [3]. Clinical characteristics of ADC included NCI (e.g., forgetfulness, loss of concentration), affective alterations (e.g., apathy) and motor system deficits [3,10,11]
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