INTRODUCTION

Neurocognitive and mental disorders persist in HIV-seropositive individuals despite antiretroviral therapy (ART) owing to the inability of ART to penetrate into the central nervous system (CNS). This incomplete CNS viral suppression leads to a chronic inflammatory state within the brain. The chapter by Wainberg et al. provides an excellent comprehensive review of both HIV-associated neurocognitive disorders (HAND) and psychiatric disorders amongst individuals with HIV infection. HAND may be seen in up to 50% of HIV-positive patients, and depression symptoms may be seen in 85% of HIV-positive individuals. The greatest factor that influences the severity of HAND is the ability of ART to effectively suppress the virus both systemically and neurologically. The most severe stage of HAND, HIV dementia is rarely seen in HIV-positive individuals on ART with suppressed virologic replication. Rather, milder stages of HAND, that is, asymptomatic neurocognitive impairment (ANI, mild neuropsychological test abnormalities without functional impairment) or mild neurocognitive disorder (MND, mild neuropsychological test abnormalities with mild functional impairment) are more commonly seen in the era of ART. Similarly, mania and psychosis are less commonly seen in HIV-positive individuals on ART. These clinical changes reflect an attenuated inflammatory state within the CNS, but this inflammatory milieu still persists in some patients, albeit to a lesser degree in ART-experienced HIV-positive individuals.

CLINICAL AND NEUROPSYCHOLOGICAL ASPECTS

HAND manifests most typically as impairments in psychomotor speed (speed of information processing), executive function (planning, multi-tasking and mental flexibility) and working memory (e.g. remembering a progressively longer span of digits). Other domains that may be affected include memory (either learning or recall) and attention. A diagnosis of HAND requires exclusion of possible confounding causes of cognitive impairment such as a prior CNS opportunistic infection, hepatitis C infection or a symptomatic traumatic brain injury [2].

As described in the chapter, psychiatric disorders are often comorbid with one another in HIV-positive individuals. It should also be noted that HAND is often comorbid with psychiatric disorders including alcohol and drug use disorders and depression. The depression symptoms may be due to the pathology of HAND involving subcortical and frontal system circuits within the brain. In evaluating an HIV-positive patient with cognitive symptoms, it is important to recognize that symptoms could be produced either from HAND or from the effects of alcohol, drug use or problems with attention resulting from depression. Such comorbid mental disorders may confound a diagnosis of HAND if they appear to be the predominant contributor to a patient’s neurocognitive impairment. However, the neuropsychological test battery required for HAND diagnosis may reveal impairment in cognitive domains that extend beyond those expected with such disorders. Thus, HAND can still be diagnosed through the presence of comorbid alcohol or drug use or depression.

EPIDEMIOLOGY OF HAND

The estimated prevalence for HAND in the current ART era is approximately 28–50% in HIV-positive individuals. Despite the rather extensive research definitions provided by the 2007 American Academy of Neurology (AAN) consensus guidelines [2], the wide variance in prevalence estimates likely reflects differences in the population samples from which the estimates are made. From these epidemiologic studies with differing demographics and virologic histories, we know that several risk factors exist for HAND. The most consistent predictor of HAND in the current era is a low nadir CD4 count_ENREF_1 [1]. Other consistent risk factors for the development of HAND that are commonly reported are low ART adherence, older age, short ART duration and the presence of cerebrovascular disease risk factors [1].