Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study

University of California, San Diego, USA.
Neurology (Impact Factor: 8.29). 12/2010; 75(23):2087-96. DOI: 10.1212/WNL.0b013e318200d727
Source: PubMed


This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART).
A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment).
Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups).
The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

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Available from: Steven Paul Woods, Oct 01, 2015
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    • "The tests were validated in Mandarin-speaking individuals within each province, using population-specific norms corrected for age, education , and sex. The global deficit score (GDS) was calculated as described (Heaton et al. 2010). Participants with a GDS <0.5 were classified as Bnot impaired,^ whereas those with GDS ≥0.5 were classified as Bimpaired.^ "
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    ABSTRACT: Factors associated with HIV-associated neurocognitive disorders (HAND) include CD4(+) nadir and count, HIV RNA level, and HIV-1 subtype. Here, we investigated demographical and clinical markers with respect to HAND in a homogenous Chinese population. Individuals with HAND (global deficit score ≥0.5) had lower nadir (p < 0.01) and CD4(+) counts (p = 0.03). HAND was also associated with AIDS (p < 0.01), but subtype was not (p = 0.198). Furthermore, worse impairment correlated with higher viral diversity (r = 0.16, p < 0.01), lower nadir (r = -0.17, p < 0.01), and CD4(+) counts (r = -0.11, p = 0.01). These remained significant even when correcting for subtype. Our findings suggest that subtype does not have a major impact on HAND.
    Journal of NeuroVirology 08/2015; DOI:10.1007/s13365-015-0377-4 · 2.60 Impact Factor
    • "Similarly, cognitive impairment among individuals with access to treatment is influenced by both HIV-related and unrelated factors. (Clifford and Ances 2013) In a recent multicenter study, the probability of cognitive impairment increased from less than 30 % among cases without confounding or contributing factors to nearly 80 % among those with such conditions, including head trauma or cerebrovascular events (Heaton et al. 2010). "
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    ABSTRACT: Cognitive impairment (CI) remains common despite access to combination antiretroviral therapy (cART); it has been linked to HIV-specific, HIV-related, and HIV-unrelated factors. Insulin resistance (IR) was associated with CI in the early cART era, when antiretroviral medications had greater mitochondrial and metabolic toxicity. We sought to examine these relationships in the current cART era of reduced antiretroviral toxicities. This study examined IR among non-diabetics in relation to a 1-h neuropsychological test battery among 994 women (659 HIV-infected and 335 HIV-uninfected controls) assessed between 2009 and 2011. The mean (standard deviation (SD)) age of the sample was 45.1 (9.3) years. The HIV-infected sample had a median interquartile range (IQR) cluster of differentiation 4 (CD4) T-lymphocyte count of 502 (310-727) cells/μL, and 54 % had undetectable plasma HIV RNA levels. Among all, the homeostasis model assessment (HOMA) of IR ranged from 0.25 to 37.14. In adjusted models, increasing HOMA was significantly associated with reduced performance on Letter-Number Sequencing (LNS) attention task (β = -0.10, p < 0.01) and on Hopkins Verbal Learning Test (HVLT) recognition (β = -0.10, p < 0.01) with weaker but statistically significant associations on phonemic fluency (β = -0.09, p = 0.01). An HIV*HOMA interaction effect was identified on the LNS attention task and Stroop trials 1 and 2, with worse performance in HIV-infected vs. HIV-uninfected women. In separate analyses, cohort members who had diabetes mellitus (DM) performed worse on the grooved pegboard test of psychomotor speed and manual dexterity. These findings confirm associations between both IR and DM on some neuropsychological tests and identify an interaction between HIV status and IR.
    Journal of NeuroVirology 03/2015; 21(4). DOI:10.1007/s13365-015-0330-6 · 2.60 Impact Factor
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    • "Along with the advent of highly active antiretroviral therapy (HAART), the incidence of HIV-associated neurocognitive disorders (HAND) has been dramatically brought down. However, approximately 50% of individuals infected with human immunodeficiency virus-1 (HIV) are reported still with HAND [1] [2] . Subjects with HAND may present deficits in multiple cognitive domains, including attention, executive function, learning, memory, and motor speed [3] [4]. "
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    ABSTRACT: This paper aimed to investigate the brain activity of human immunodeficiency virus (HIV) positive patients with normal cognition during unilateral hand movement and whether highly active antiretroviral therapy (HAART) could affect the brain function. Functional magnetic resonance imaging (fMRI) was performed for 60 HIV positive (HIV+) subjects and –42 healthy age-matched right-handed control subjects. Each subject was evaluated by the neuropsychological test and examined with fMRI during left and right hand movement tasks. HIV+ subjects showed greater activation in anterior cingulum, precuneus, occipital lobes, ipsilateral postcentral gyrus and contralateral cerebellum compared with control group during right hand movement task. However, during left hand movement no statistically significant difference was detected between these two groups. HAART medication for HIV+ subjects lowered the increased activity to normal level. Meanwhile patients receiving the regimen of zidovudine, lamivudine and efavirenz showed lower activity at bilateral caudate and ipsilateral inferior frontal gyrus in comparison with subjects receiving other HAART regimens. Therefore, HIV+ subjects demonstrated brain asymmetry in motor cortex, with increased activity present during right hand movement but absent during left hand movement. HAART proves effective in HIV+ subjects even with normal cognition and the specific regimen of HAART could prevent cerebral abnormal functions. Meanwhile, this study validates that during motor tasks, fMRI can detect the brain signal changes prior to the occurrences of other HIV- associated dysfunctions.
    03/2015; 1(2). DOI:10.1016/j.jrid.2015.02.009
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