Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. 

We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. 

We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD-standard deviation-3.7). 

A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. 

Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. 

Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.

Full article at:  http://goo.gl/vb0hz3

By:  Focà E1, Magro P2, Motta D3, Compostella S4, Casari S5, Bonito A6, Brianese N7, Ferraresi A8, Rodari P9, Pezzoli MC10, Quiros-Roldan E11, Castelli F12.

• 1Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. emanuelefoca@gmail.com.
• 2Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. p.magro@unibs.it.
• 3Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. davide.motta84@gmail.com.
• 4Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. compostar@hotmail.com.
• 5Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. s.casari@infettivibrescia.it.
• 6Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. andreabonito@hotmail.com.
• 7Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. nigri_bri@libero.it.
• 8Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. alice-ferraresi@hotmail.it.
• 9Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. paolarodari@icluod.com.
• 10Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. chiarapezzoli@yahoo.com.
• 11Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. eugeniaquiros@yahoo.it.
• 12Department of Infectious and Tropical Diseases, University of Brescia and Brescia Spedali Civili General Hospital, Piazzale Spedali Civili 1, 25123 Brescia, Italy. francesco.castelli@unibs.it. 
• Int J Mol Sci. 2016 Mar 24;17(4). pii: E434. doi: 10.3390/ijms17040434.

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Neurometabolite Alterations Associated with Cognitive Performance in Perinatally HIV-Infected Children

Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. 

This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36).Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses.HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. 

There were no associations between neurometabolites and neuronal damage markers in blood or CSF.Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.

Below:  Exemplar planning of chemical shift imaging (CSI), superimposed on a 3D-T1-weighted image. Based on the 3D-T1-weighted scan (A), gray matter (GM), and white matter (WM) segmentation was performed within the CSI field-of-view (B). Estimated metabolite levels (C) were averaged within all GM and WM voxels to obtain mean GM and WM values (D). CSI = chemical shift imaging, GM = gray matter, WM = white matter.

Full article at:   http://goo.gl/cfpC6B

By:  Van Dalen YW1, Blokhuis C, Cohen S, Ter Stege JA, Teunissen CE, Kuhle J, Kootstra NA, Scherpbier HJ, Kuijpers TW, Reiss P, Majoie CB, Caan MW, Pajkrt D.

• 1From the Department of Pediatric Hematology, Immunology and Infectious Diseases, (YWVD, CB, SC, JATS, HJS, TWK, DP); Psychosocial Department (JATS), Emma Children's Hospital/Academic Medical Center; Neurochemistry Laboratory and Biobank (CET), Department of Clinical Chemistry, VU University Medical Center and Neurocampus Amsterdam, the Netherlands; Neurology (JK), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland; Department of Experimental Immunology (NAK); Department of Global Health and Amsterdam Institute of Global Health and Development (PR), Academic Medical Center; HIV Monitoring Foundation (PR); Department of Internal Medicine (PR), Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA); and Department of Radiology (CBLMM, MWAC), Academic Medical Center, Amsterdam, the Netherlands. 
• Medicine (Baltimore). 2016 Mar;95(12):e3093. doi: 10.1097/MD.0000000000003093.

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Association of Caregiver Quality of Care with Neurocognitive Outcomes in HIV-Affected Children Aged 2-5 Years in Uganda

Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. 

This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver-child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver-child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. 

Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. 

As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. 

Our results support the view of program guidance for HIV-affected children that suggest family-oriented care with emphasis on parent-child relationships for optimal child development.

Purchase full article at:   http://goo.gl/m6RYmt

By:  Bass JK1, Nakasujja N2, Familiar-Lopez I3, Sikorskii A4, Murray SM1, Opoka R5, Augustinavicius J1, Boivin MJ3.

• 1 Department of Mental Health , Johns Hopkins Bloomberg School of Public Health , Baltimore , MD , USA.
• 2 Department of Psychiatry , Makerere University , Kampala , Uganda.
• 3 Department of Psychiatry , Michigan State University , East Lansing , MI , USA.
• 4 Department of Statistics and Probability , Michigan State University , East Lansing , MI , USA.
• 5 Department of Paediatrics & Child Health , Makerere University , Kampala , Uganda.
• AIDS Care. 2016 Feb 17:1-8. 

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Impaired Executive Function in 14- to 16-Year-Old Boys with Conduct Disorder Is Related to Recidivism

BACKGROUND:

Several studies have suggested a relationship between cognitive impairment and recidivism, but most have adopted a retrospective design.

AIM:

The aim of this study was to test for any relationship between impaired executive function in adolescents with conduct disorder and subsequent recidivism up to 3 years later.

METHOD:

In this prospective cohort study, 221 male adolescents with conduct disorder, admitted to a juvenile justice assessment centre for the first time, were interviewed about their offence, age, onset of delinquency and family history. They completed the Wisconsin Card Sorting Test (Keio version) (KWCST) and the Iowa gambling task. Scores were compared between those who subsequently re-offended and those who did not.

RESULTS:

Seventy-six (34%) participants re-offended. There was no direct difference between groups in executive function, but there were age differences both in executive function and in recidivism. Multivariate logistic regression analysis indicated that the variables, which were independently associated with recidivism, were younger age, change in the person who brought up the child, and fewer (≤4) categories achieved on the KWCST. Recidivists were about twice as likely as single offenders to have achieved four categories or less on the KWCST (odds ratio 2.2, 95% confidence interval 1.1-4.4).

CONCLUSIONS:

Impaired executive function appears to predispose to recidivism among young first-time male offenders with conduct disorder. Our findings also suggest that further precise assessments of environmental stress on developing neurocognitive function could clarify the background of antisocial behaviour.

Purchase full article at:   http://goo.gl/J1qyp6

By:  Miura H1,2, Fuchigami Y1.

• 1Nagoya Juvenile Classification Home, Nagoya, Aichi, Japan.
• 2Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. 
• Crim Behav Ment Health. 2016 Feb 10. doi: 10.1002/cbm.1993. 

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HIV and Cognitive Concerns - Video

Via:  http://www.ohtn.on.ca/

Combined Effects of HIV & Marijuana Use on Neurocognitive Functioning & Immune Status

The current study examined the independent and combined effects of HIV and marijuana (MJ) use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. 

MJ users consisted of individuals who reported regular use of MJ for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n = 55) and HIV- (n = 34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported MJ use. 

Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. 

• HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, 
• and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. 
• Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV- moderate-to-heavy users as well as all other comparison groups. 
• In the domain of verbal fluency, HIV+ light users outperformed HIV- light users, 
• but no HIV group differences were observed at other MJ use levels. 
• HIV+ MJ users demonstrated lower viral load and higher CD4 count than non-users. 

The current study findings extend the literature by demonstrating the complex relationship between HIV status and MJ use on neurocognitive and clinical outcomes.

Purchase full article at:   http://goo.gl/kQWn5m

By:   Thames AD1, Mahmood Z1, Burggren AC1, Karimian A1, Kuhn TP1.

1 Department of Psychiatry and Biobehavioral Sciences , University of California, Los Angeles , Los Angeles , CA , USA.

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The Impact of Ethnicity/Race on the Association Between the Veterans Aging Cohort Study (VACS) Index & Neurocognitive Function among HIV-Infected Persons

The Veterans Aging Cohort Study (VACS) Index was developed as a risk index for health outcomes in HIV, and it has been consistently associated with mortality. It shows a significant, yet relatively weak, association with neurocognitive impairment, and little is known about its utility among ethnic/racial minority groups. 

We examined whether the association between the VACS Index and neurocognition differed by ethnic/racial group. Participants included 674 HIV-infected individuals (369 non-Hispanic whites, 111 non-Hispanic blacks, and 194 Hispanics). 

Neurocognitive function was assessed via a comprehensive battery. Scaled scores for each neurocognitive test were averaged to calculate domain and global neurocognitive scores. Models adjusting for demographics and HIV disease characteristics not included in the VACS Index showed that higher VACS Index scores (indicating poorer health) were significantly associated with worse global neurocognition among non-Hispanic whites. This association was comparable in non-Hispanic blacks, but nonsignificant among Hispanics (with similar results for English and Spanish speaking). 

We obtained comparable findings in analyses adjusting for other covariates (psychiatric and medical comorbidities and lifestyle factors). Analyses of individual neurocognitive domains showed similar results in learning and delayed recall. For other domains, there was an effect of the VACS Index and no significant interactions with race/ethnicity. Different components of the VACS Index were associated with global neurocognition by race/ethnicity. 

In conclusion, the association between the VACS Index and neurocognitive function differs by ethnic/racial group. Identifying key indicators of HIV-associated neurocognitive impairment by ethnic/racial group might play an important role in furthering our understanding of the biomarkers of neuroAIDS.

Purchase full article at:   http://goo.gl/oxoIHo

By:   Marquine MJ1, Sakamoto M2, Dufour C3, Rooney A2, Fazeli P4, Umlauf A2, Gouaux B2, Franklin D2, Ellis R5, Letendre S3, Cherner M2, Heaton RK2, Grant I2,Moore DJ2; HNRP Group.

• 1Department of Psychiatry, University of California, San Diego, CA, USA. mmarquine@ucsd.edu.
• 2Department of Psychiatry, University of California, San Diego, CA, USA.
• 3Department of Medicine, University of California, San Diego, CA, USA.
• 4Psychology Department, University of Alabama, Birmingham, CA, USA.
• 5Department of Neurosciences, University of California, San Diego, CA, USA. 

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Effects of HIV & Childhood Trauma on Brain Morphometry & Neurocognitive Function

A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. 

The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. 

This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.

Purchase full article at: http://goo.gl/GbMtvq

By: Spies G1,2, Ahmed-Leitao F3, Fennema-Notestine C4,5, Cherner M4, Seedat S3,6.

• 1South African Research Chairs Initiative (SARChI), PTSD program, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. ggiocos@sun.ac.za.
• 2Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. ggiocos@sun.ac.za.
• 3South African Research Chairs Initiative (SARChI), PTSD program, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
• 4Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
• 5Department of Radiology, University of California San Diego, La Jolla, CA, USA.
• 6MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa. 

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Long-Term Efavirenz Use Is Associated with Worse Neurocognitive Functioning in HIV-Infected Patients

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.

Via:  http://ht.ly/SU2nK Purchase full article at: http://goo.gl/sPbu8l

By: Ma Q1,2, Vaida F3, Wong J3, Sanders CA3, Kao YT3, Croteau D3, Clifford DB4, Collier AC5, Gelman BB6, Marra CM5, McArthur JC7, Morgello S8, Simpson DM8,Heaton RK3, Grant I3, Letendre SL9; CHARTER Group.

• 1University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA
• 2Department of Pharmacy Practice, University at Buffalo, 315 Kapoor Hall, Buffalo, NY, 14214, USA
• 3University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
• 4Washington University, St. Louis, MO, USA.
• 5University of Washington, Seattle, WA, USA.
• 6University of Texas Medical Branch, Galveston, TX, USA.
• 7Johns Hopkins University, Baltimore, MD, USA.
• 8Mount Sinai School of Medicine, New York, NY, USA.
• 9University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA

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