Article

Screening for Cognitive Impairment in Human Immunodeficiency Virus

Memory and Aging Center, Department of Neurology, University of California–San Francisco, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 10/2011; 53(8):836-42. DOI: 10.1093/cid/cir524
Source: PubMed

ABSTRACT

Recent publications estimate the prevalence of human immunodeficiency virus (HIV)–associated neurocognitive disorders (HAND)
exceeds 50%, and this rate is likely higher among older patients. Cognitive impairment may impact medication adherence, and
symptomatic impairment has been linked to all-cause mortality providing some impetus for early detection. There are currently
insufficient data to inform solid recommendations on screening methods. Most HIV-specific tools have poor performance characteristics
for all but the most severe form of impairment, which accounts for <5% of cases. Reliance on symptoms is likely to miss a
substantial proportion of individuals with HAND due to poor insight, confounding mood disturbances, and lack of well-informed
proxies. In the aging HIV-positive population, broader screening tools may be required to allow sensitivity for both HIV and
neurodegenerative disorders. We describe the clinical presentation of HAND, review existing data related to screening tools,
and provide preliminary and practical recommendations in the absence of more definitive studies.

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    • "Despite advances in potent combination antiretroviral therapy (ART), milder forms of HIV-associated neurocognitive disorders (HAND) continue to affect nearly 50 % of HIV-infected individuals, suggesting that either current clinical management of HAND is inadequate, or HAND is irreversible , or both (Letendre 2011; Valcour et al. 2011). The pathogenesis of HAND remains incompletely understood. "
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    ABSTRACT: Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p < 0.001), were less likely to have AIDS (p < 0.001) or hepatitis C virus (HCV) coinfection (p < 0.05), had higher CD4+ T cell nadirs (p < 0.001), had lower peak (p < 0.001) and current (p < 0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p < 0.001). Overall, EFV users had worse speed of information processing (p = 0.04), verbal fluency (p = 0.03), and working memory (p = 0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n = 329), EFV users performed poorly, whereas among HCV seropositives (n = 116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n = 269), EFV users had worse speed of information processing (p = 0.02) and executive functioning (p = 0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial.
    No preview · Article · Sep 2015 · Journal of NeuroVirology
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    • "Tools for assessing neurocognitive disorders include a variety of established, as well as emerging, technologies that include neurocognitive testing batteries, neuroimaging, and biomarkers [29, 36, 45,47484950515253545556. This review will highlight some of the challenges and controversies that make assessment and diagnosis of neurocognitive disorders in HIVinfected persons a complex process that will necessitate revised strategies. "
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    ABSTRACT: The prevalence of HIV (human immunodeficiency virus) associated neurocognitive disorders (HAND) will undoubtedly increase with the improved longevity of HIV-infected persons. HIV infection, itself, as well as multiple physiologic and psychosocial factors can contribute to cognitive impairment and neurologic complications. These comorbidities confound the diagnosis, assessment, and interventions for neurocognitive disorders. In this review, we discuss the role of several key comorbid factors that may contribute significantly to the development and progression of HIV-related neurocognitive impairment, as well as the current status of diagnostic strategies aimed at identifying HIV-infected individuals with impaired cognition and future research priorities and challenges.
    Full-text · Article · Mar 2015
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    • "HIV-associated neurocognitive disorders (HAND) are a common complication of HIV infection in the era of combined antiretroviral therapy (cART) that independently predict overall morbidity and mortality (Ellis et al. 2007; Ellis et al. 1997; Valcour et al. 2011; Vivithanaporn et al. 2010). The clinical sub-syndromes of HAND vary in severity of cognitive impairment and associated functioning and include asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD) (Antinori et al. 2007). "
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    ABSTRACT: HIV-associated neurocognitive disorders (HAND) affect up to 50 % of HIV-infected adults, independently predict HIV morbidity/mortality, and are associated with neuronal damage and monocyte activation. Cerebrospinal fluid (CSF) neurofilament subunits (NFL, pNFH) are sensitive surrogate markers of neuronal damage in several neurodegenerative diseases. In HIV, CSF NFL is elevated in individuals with and without cognitive impairment, suggesting early/persistent neuronal injury during HIV infection. Although individuals with severe cognitive impairment (HIV-associated dementia (HAD)) express higher CSF NFL levels than cognitively normal HIV-infected individuals, the relationships between severity of cognitive impairment, monocyte activation, neurofilament expression, and systemic infection are unclear. We performed a retrospective cross-sectional study of 48 HIV-infected adults with varying levels of cognitive impairment, not receiving antiretroviral therapy (ART), enrolled in the CNS Anti-Retroviral Therapy Effects Research (CHARTER) study. We quantified NFL, pNFH, and monocyte activation markers (sCD14/sCD163) in paired CSF/plasma samples. By examining subjects off ART, these correlations are not confounded by possible effects of ART on inflammation and neurodegeneration. We found that CSF NFL levels were elevated in individuals with HAD compared to cognitively normal or mildly impaired individuals with CD4+ T-lymphocyte nadirs ≤200. In addition, CSF NFL levels were significantly positively correlated to plasma HIV-1 RNA viral load and negatively correlated to plasma CD4+ T-lymphocyte count, suggesting a link between neuronal injury and systemic HIV infection. Finally, CSF NFL was significantly positively correlated with CSF pNFH, sCD163, and sCD14, demonstrating that monocyte activation within the CNS compartment is directly associated with neuronal injury at all stages of HAND.
    Full-text · Article · Mar 2015 · Journal of NeuroVirology
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