Simioni S, Cavassini M, Annoni JM, et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. : 24:; 1243-50

Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
AIDS (London, England) (Impact Factor: 5.55). 12/2009; 24(9):1243-50. DOI: 10.1097/QAD.0b013e3283354a7b
Source: PubMed


To determine the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV-positive patients. To evaluate the relevance of the HIV dementia scale to detect HANDs.
Assessment of HANDs with neuropsychological tests.
Two hundred HIV-infected patients with undetectable HIV-1 RNA concentrations in the plasma, no history of major opportunistic infection of the central nervous system in the past 3 years, no current use of intravenous drugs, and no major depression answered a questionnaire designed to elicit cognitive complaints. Cognitive functions of 50 complaining and 50 noncomplaining HIV-positive patients were assessed.
Patients had undetectable HIV-1 RNA concentrations for a median time of 48 months (range 3.2-136.6). The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints (asymptomatic neurocognitive impairment 24%, mild neurocognitive disorders 52%, and HIV-associated dementia 8%) and 64% among noncomplainers (asymptomatic neurocognitive impairment 60%, mild neurocognitive disorders 4%, and HIV-associated dementia 0%; P < 0.001). A score of 14 points or less on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in noncomplainers.
The prevalence of HANDs is high even in long-standing aviremic HIV-positive patients. However, HANDs without functional repercussion in daily life (asymptomatic neurocognitive impairment) is the most frequent subtype observed. In this population, the HIV dementia scale with a cutoff of 14 points or less seems to provide a useful tool to screen for the presence of HANDs.

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    • "With the advent of combined antiretroviral therapy (CART), the incidence of HAD has dramatically decreased (Dore et al. 2003). However , the incidence of milder forms of cognitive impairment appears to remain high (Robertson et al. 2007; Simioni et al. 2010; Tozzi et al. 2005). The exact reasons behind the continuing prevalence of milder forms of HAND are not clear. "
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    ABSTRACT: In the era of combined antiretroviral therapy (CART), many of the complications due to HIV-1 infection have diminished. One exception is HIV-associated neurocognitive disorder (HAND). HAND is a spectrum of disorders in cognitive function that ranges from asymptomatic disease to severe dementia (HAD). The milder form of HAND has actually remained the same or slightly increased in prevalence in the CART era. Even in individuals who have maintained undetectable HIV RNA loads, viral proteins such as Nef and Tat can continue to be expressed. In this report, we show that Nef protein and nef messenger RNA (mRNA) are packaged into exosomes that remain in circulation in patients with HAD. Plasma-derived Nef exosomes from patients with HAD have the ability to interact with the neuroblastoma cell line SH-SY5Y and deliver nef mRNA. The mRNA can induce expression of Nef in target cells and subsequently increase expression and secretion of beta-amyloid (Aβ) and Aβ peptides. Increase secretion of amyloid peptide could contribute to cognitive impairment seen in HAND.
    Journal of NeuroVirology 09/2015; DOI:10.1007/s13365-015-0383-6 · 2.60 Impact Factor
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    • "While the introduction of combination antiretroviral therapy (cART) has significantly reduced the incidence of HIV-associated dementia (HAD) — the most severe form of HIV-associated neurocognitive disorders (HAND) (McArthur et al., 1999; McArthur, 2004), the overall prevalence of HAND has remained high (Harezlak et al., 2011; Heaton et al., 2011, 2010; Schouten et al., 2011; Simioni et al., 2010). It has been suggested that about 30–60% of HIV-positive adults are currently living with HAND (Grant, 2008), and more than half of these individuals have the mildest form of HAND referred to as asymptomatic neurocognitive impairment (ANI) (Heaton et al., 2010). "
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    ABSTRACT: In the post combination antiretroviral therapy (cART) era, the prevalence of mild forms of HIV-associated neurocognitive disorders (HAND) in individuals with HIV-infection remains high. There is a pressing need to find biomarkers that can aid clinical assessment of HAND, especially in those with mild or no neurocognitive symptoms. Here we hypothesized that a reduction in neural specificity, or the specificity of neuronal tuning, could serve as a potential biomarker of asymptomatic HAND. To directly test this hypothesis, we applied two advanced fMRI techniques to examine the difference in neural specificity between middle-aged HIV+ women and age-matched negative controls, with a focus on the fusiform face area (FFA), a critical region in face processing. Face discrimination performance was assessed outside of the scanner. While the behavioral performance of face discrimination was comparable between the two groups, a reduced neural specificity in the FFA of HIV-positive women was revealed by a novel fMRI analysis technique, local regional heterogeneity analysis, or Hcorr , as well as an established technique, fMRI-rapid adaptation. In contrast, conventional fMRI techniques were insensitive to these early changes. These results suggest that, prior to the onset of detectable behavioral deficits, significant neuronal dysfunctions are already present in HIV+ individuals, and these early neuronal dysfunctions can be detected and assessed via neural specificity, which, in combining with the novel Hcorr technique, has a strong potential to serve as a biomarker of asymptomatic HAND and other neurodegenerative diseases.
    Clinical neuroimaging 12/2014; 8. DOI:10.1016/j.nicl.2014.12.003 · 2.53 Impact Factor
    • "Combination antiretroviral therapy (cART) has shifted the nature of human immunodefiency virus (HIV)-infection from a terminal illness to a chronic manageable condition with a life expectancy that has gradually approached that of seronegative persons [Antiretroviral Therapy Cohort Collaboration, 2008; Nakagawa et al., 2013]. However , HIV-infected patients remain at a significantly increased risk of developing HIV-associated neurocognitive disorders (HAND), with 35–70% of all patients (treated and untreated) exhibiting at least subtle impairments on tests of neuropsychological function [Antinori et al., 2007; Cysique and Brew, 2009; Gannon et al., 2011; Heaton et al., 2010, 2011; Robertson et al., 2007; Sacktor et al., 2002; Simioni et al., 2010; Tozzi et al., 2007]. Patients with HAND are more likely to be unemployed, have greater problems with medication adherence, and have lower quality of life [Albert et al., 1995; Heaton et al., 1994, 2004; Kaplan et al., 1995; Marcotte et al., 2004; van Gorp et al., 1999]. "
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    ABSTRACT: Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker.
    Human Brain Mapping 11/2014; 36(3). DOI:10.1002/hbm.22674 · 5.97 Impact Factor
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