East African HIV care: depression and HIV outcomes.

Importance:Depression is a common co-morbidity for people living with HIV (PLWH) and is associated with elevated plasma HIV RNA levels. While depression correlates with deficits in antiretroviral (ARV) adherence, little data exist to inform the relationship between depression and HIV vial load more broadly. Objective:To examine the relationship between depression and viral load in the African Cohort Study (AFRICOS) independently of ARV adherence. Design:PLWH in Kenya, Uganda and Tanzania underwent screening for depression using the Center for Epidemiologic Studies Depression Scale (CESD) upon enrollment at AFRICOS HIV care sites. Setting:AFRICOS is an ongoing prospective longitudinal cohort study enrolling HIV-infected adults at HIV care centers including sites in Kenya, Tanzania and Uganda. These sites are administered by President's Emergency Plan For AIDS Relief programs. Participants:HIV+ individuals were eligible if they were at least 18 years old, receiving HIV care at the enrolling clinic and consented to data and specimen collection. Main outcome measure:CESD. Results:Among 2307 participants, 18-25% met the CESD threshold for depression. Depression was associated with decreased ARV adherence (OR 0.59, p =  0.01). Higher scores on three CESD items were significantly associated with 209-282% higher viral load, independently of ARV adherence among participants on ARVs ⩾6 months. Conclusions:PLWH had high prevalence of depression on the CESD. Diverse depression symptoms were independently associated with increases in viral load, underscoring the need for comprehensive treatment of depression

Variability in C-reactive protein is associated with cognitive impairment in women living with and without HIV: a longitudinal study

Despite the availability of effective antiretroviral therapies, cognitive impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence from primarily cross-sectional studies, in predominantly male samples, implicates monocyte- and macrophage-driven inflammatory processes linked to HIV-associated CI. Thus, peripheral systemic inflammatory markers may be clinically useful biomarkers in tracking HIV-associated CI. Given sex differences in immune function, we focused here on whether mean and intra-individual variability in inflammatory marker-predicted CI in HIV+ and HIV− women. Seventy-two HIV+ (36 with CI) and 58 HIV− (29 with CI) propensity-matched women participating in the Women’s Interagency HIV Study completed a neuropsychological battery once between 2009 and 2011, and performance was used to determine CI status. Analysis of 13 peripheral immune markers was conducted on stored biospecimens at three time points (7 and 3.5 years before neuropsychological data collection and concurrent with data collection). HIV+ women showed alterations in 8 immune markers compared to HIV− women. The strongest predictors of CI across HIV+ and HIV− women were lower mean soluble tumor necrosis factor receptor I (sTNFRI) levels, higher mean interleukin (IL)-6 levels, and greater variability in C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 (p values < 0.05). Stratified by HIV, the only significant predictor of CI was greater variability in CRP for both HIV+ and HIV− women (p values < 0.05). This variability predicted lower executive function, attention/working memory, and psychomotor speed in HIV+ but only learning in HIV− women (p values < 0.05). Intra-individual variability in CRP levels over time may be a good predictor of CI in predominately minority low-socioeconomic status midlife women

Pathogenesis of HIV in the Central Nervous System

HIV can infect the brain and impair central nervous system (CNS) function. Combination antiretroviral therapy (cART) has not eradicated CNS complications. HIV-associated neurocognitive disorders (HAND) remain common despite cART, although attenuated in severity. This may result from a combination of factors including inadequate treatment of HIV reservoirs such as circulating monocytes and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant use, and factors associated with prescribed drugs, including antiretrovirals. This review highlights recent investigations of HIV-related CNS injury with emphasis on cART-era neuropathological mechanisms in the context of both US and international settings

Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women

Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αβ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study

Background: HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. / Methods: We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. / Results: LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. / Conclusions: In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver of systemic and CNS inflammation. However, LPS was not detectable in the CSF, and since sCD14 is a marker of monocyte activation sCD14 may be increased due to other causes than microbial translocation. Further studies regarding cognitive impairment and biomarkers are warranted to fully understand causality

Can an EASYcare based dementia training programme improve diagnostic assessment and management of dementia by general practitioners and primary care nurses? The design of a randomised controlled trial

Contains fulltext : 70099.pdf ( ) (Open Access)BACKGROUND: Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses. METHODS: The DTP is a complex educational intervention that consists of two workshops, a coaching program, access to an internet forum, and a Computerized Clinical Decision Support System on dementia diagnostics. One hundred duos of GPs and nurses will be recruited, from which 2/3 will be allocated to the intervention group and 1/3 to the control group. The effects of implementation of the DTP will be studied in a cluster-randomised controlled trial. Primary outcomes will be the number of cognitive assessments and dementia diagnoses in a period of 9 months following workshop participation. Secondary outcomes are measured on GP and nurse level: adherence to national guidelines for dementia, attitude, confidence and knowledge regarding dementia diagnosis and management; on patient level: number of emergency calls, visits and consultations and patient satisfaction; and on caregiver level: informal caregiver burden and satisfaction. Data will be collected from GPs' electronic medical records, self-registration forms and questionnaires. Statistical analysis will be performed using the MANOVA-method. Also, exploratory analyses will be performed, in order to gain insight into barriers and facilitators for implementation and the possible causal relations between the rate of success of the intervention components and the outcomes. DISCUSSION: We developed multifaceted dementia training programme. Novelties in this programme are the training in fixed collaborative duos and the inclusion of an individual coaching program. The intervention is designed according to international guidelines and educational standards. Exploratory analysis will reveal its successful elements. Selection bias and contamination may be threats to the reliability of future results of this trial. Nevertheless, the results of this trial may provide useful information for policy makers and developers of continuing medical education. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00459784

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

<p>Abstract</p> <p>Background</p> <p>Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging.</p> <p>Methods</p> <p>Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations.</p> <p>Results</p> <p>Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race.</p> <p>Conclusion</p> <p>The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.</p

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

<p>Abstract</p> <p>Background</p> <p>Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.</p> <p>Methods</p> <p>In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ_1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.</p> <p>Results</p> <p>CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ_1-42in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.</p> <p>Conclusions</p> <p>Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.</p