HIV-associated neurocognitive disorders

Payal B Patel MD (

Dr. Patel of Yale University has no relevant financial relationships to disclose.

)
Christina M Marra MD, editor. (

Dr. Marra of the University of Washington School of Medicine owned stock in Johnson & Johnson and McKesson within the past 12 months.

)
Originally released April 1, 1994; last updated August 21, 2019; expires August 21, 2022

This article includes discussion of HIV-associated neurocognitive disorders, HIV-associated dementia, HIV-associated asymptomatic neurocognitive impairment, and HIV-associated mild neurocognitive disorder. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

In this review, we will describe the history of HIV-associated neurocognitive disorders (HAND), an umbrella term that includes memory, processing speed, and concentration and attentional deficits in individuals living with HIV, important terminology and classification systems used to diagnose HIV-associated neurocognitive disorders, and the clinical manifestations and management of HIV-associated neurocognitive disorders.

Key points

 

• HIV-associated neurocognitive disorder is a clinical syndrome with varied presentation of cognitive impairment and clinical fluctuation that occurs in associated with or as a primary manifestation of HIV infection.

 

• Combination antiretroviral therapy has resulted in improved survival of HIV-infected individuals. This, in combination with the compound effects of age-related cognitive changes in individuals affected by HIV, has resulted in an increasing prevalence of cognitive impairment in individuals living with HIV.

 

• Recommended approaches for diagnosis of HIV-associated neurocognitive disorder allow for the categorization of individuals ranging from mild to severe cognitive impairment with or without impairment in activities of daily living. These categories have important prognostic implications.

 

• Effective control of HIV viral replication with combination antiretroviral therapy is an important management tool for HIV-associated neurocognitive disorders but may not be sufficient for prevention of neurocognitive impairment or decline in individuals living with HIV.

Historical note and terminology

Prior to antiretroviral therapy (1980-1990s). Following the discovery of HIV and the most severe manifestation of HIV, AIDS (or acquired immunodeficiency syndrome), Navia and Price subsequently introduced the term "AIDS dementia complex" (Navia and Price 1987), which referred to cognitive, behavioral, and motor deficits that occurred frequently in patients living with AIDS. The term "HIV encephalopathy" was added to the list of terms used to describe neurologic features associated with AIDS dementia complex (Levy and Bredesen 1988).

In 1991, the American Academy of Neurology AIDS Task Force developed definitional criteria for AIDS dementia (Janssen et al 1991). The terms "AIDS dementia complex," "HIV dementia," and "HIV encephalopathy," and "HIV-1-associated cognitive/motor complex" were considered are synonymous conditions. Before antiretroviral therapy was available, 20% to 30% of patients with severe HIV disease experienced HIV-associated dementia, the most severe cognitive complication associated with HIV (Gonzalez-Scarano and Martin-Garcia 2005; Kaul and Lipton 2005).

After discovery of and increased accessibility to antiretroviral therapy (1996 and beyond). With the introduction of highly active antiretroviral therapy the incidence of HIV-associated dementia, the most severe form of HIV-associated neurocognitive disorders, has decreased but the absolute prevalence of HIV-associated neurocognitive disorder has increased every decade given the longer life expectancy of individuals with HIV on combination antiretroviral therapy. Approximately 40% of HIV-infected patients have some degree of HIV-associated neurocognitive impairment (Sacktor et al 2001; Sacktor 2002; McArthur 2004; Antinori et al 2007) and the incidence of neurocognitive impairment in HIV-infected individuals has remained stable from the pre-antiretroviral therapy to post-antiretroviral therapy era (Heaton et al 2011).

In 2007, Antinori and colleagues developed classification criteria to standardize nomenclature surrounding neurocognitive diagnosis in persons living with HIV (PLWH). The Frascati criteria consist of 3 separate clinical entities (Antinori et al 2007) and are detailed in Table 1. Asymptomatic neurocognitive impairment includes individuals with cognitive performance 1 standard deviation below the mean in 2 or more cognitive domains without documented impairment in activities of daily living. Mild neurocognitive disorder includes individuals with cognitive performance 1 standard deviation below the mean in 2 or more cognitive domains with mild documented difficulties in activities of daily living. HIV-associated dementia includes those with cognitive performance falling 2 standard deviations below the mean in 2 or more domains and severe difficulties in performance of activities of daily living. Other confounding factors or non-HIV related diagnoses must be excluded in order to attribute cognitive impairment to the underlying HIV infection. These alternative diagnoses may include substance abuse, other causes of dementia, or pseudo-dementia associated with an underlying psychiatric condition. A key point of differentiation is between asymptomatic neurocognitive impairment and symptomatic disorders (mild neurocognitive disorder and HIV-associated dementia), which differ based on impairment in activities of daily living.

Table 1. Frascati Criteria for Diagnosis of HIV-Associated Neurocognitive Disorders

HIV-associated asymptomatic neurocognitive impairment*

 

(1) Two or more neurocognitive domains** with performance at least 1.0 SD below the mean for age and education-appropriate norms on standardized neuropsychological tests.

 

(2) No impact on everyday function.

 

(3) No evidence of alternative diagnoses or delirium.

HIV-associated mild neurocognitive disorder*

 

(1) Two neurocognitive domains** with performance at least 1.0 SD below the mean for age and education appropriate norms on standardized neuropsychological tests.

 

(2) The cognitive impairment mildly interferes with activities of daily living.

 

(3) No evidence of alternative diagnoses or delirium.

HIV-associated dementia*

 

(1) Two neurocognitive domains** with performance at least 2.0 SD below the mean for age and education appropriate norms on standardized neuropsychological tests.

 

(2) The cognitive impairment significantly interferes with activities of daily living.

 

(3) No evidence of an alternative diagnoses or delirium.

*If there is a prior diagnosis of HIV-associated neurocognitive disorder but currently the individual does not meet criteria, the diagnosis of HIV-associated neurocognitive disorder in remission can be made.

**The neuropsychological assessment must survey at least the following abilities: verbal/language; attention/working memory; abstraction/executive; memory (learning, recall); speed of information processing; sensory-perceptual, motor skills.

Since the advent of antiretroviral therapy, most patients present with mild forms of HIV-associated neurocognitive disorder resulting in a shift from severe to milder HIV-associated neurocognitive disorder subtypes in the posttreatment era (Sacktor et al 2004). Milder forms of HIV-associated neurocognitive disorder have important prognostic implications, as individuals with asymptomatic neurocognitive impairment have an increased risk of meeting criteria for symptomatic impairment (mild neurocognitive disorder and HIV-associated dementia) over the next few years (Grant et al 2014). Although only a small subset of patients may progress to frank dementia, even patients with the mildest of symptoms can have their quality of life affected by disruption in their ability to perform activities of daily living and, importantly, in their adherence to medication (McArthur 2004).

The term "HIV encephalitis" should be reserved for the pathological features of multinucleated giant cell encephalitis with HIV identified in the brain and not used to describe the clinical syndrome. Similarly, although HIV-associated dementia can develop concurrently with other HIV-associated neurologic disorders, such as myelopathy and neuropathy, these diseases are discrete clinical entities separate from HAND with distinct manifestations, courses, and pathogenic mechanisms.

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