Dataset Information

Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy.

ABSTRACT: OBJECTIVE:Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloid-lineage. Here, we aimed to understand the contribution of activated microglia located in vulnerable brain regions (e.g. frontal, subcortical) of HIV-infected, virally suppressed (HIV+VS) individuals in relation to cognitive and motor function. DESIGN:Twenty-one HIV+VS individuals underwent PET with [11C]DPA-713 to image the translocator protein 18?kDa (TSPO), a marker of microglial activation, and completed a comprehensive neuropsychological test battery. METHODS:Multivariable linear regressions were used to examine the contribution of [11C]DPA-713 binding to cognitive performance. RESULTS:Higher [11C]DPA-713 binding was associated with lower cognition among HIV+VS individuals. [11C]DPA-713 binding in middle frontal gyrus/frontal cortex, hippocampus/temporal cortex and occipital cortex was inversely associated with performance on a number of cognitive domains, including verbal memory, processing speed/attention/concentration, executive function, working memory and motor function. [C]DPA-713 binding in parietal cortex, cerebellum and thalamus was associated with only specific cognitive domains including visual construction and verbal memory. Binding was not associated with global cognitive performance. CONCLUSION:The findings add to the growing body of evidence that immune-mediated brain injury may contribute to domain specific, HIV-associated, cognitive vulnerabilities despite viral suppression.

SUBMITTER: Rubin LH

PROVIDER: S-EPMC6314298 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy.

Rubin Leah H LH Sacktor Ned N Creighton Jason J Du Yong Y Endres Christopher J CJ Pomper Martin G MG Coughlin Jennifer M JM

AIDS (London, England) 20180701 12

<h4>Objective</h4>Despite viral suppression, HIV-associated cognitive impairment persists and may be partially due to persistent immune signalling by cells of the myeloid-lineage. Here, we aimed to understand the contribution of activated microglia located in vulnerable brain regions (e.g. frontal, subcortical) of HIV-infected, virally suppressed (HIV+VS) individuals in relation to cognitive and motor function.<h4>Design</h4>Twenty-one HIV+VS individuals underwent PET with [11C]DPA-713 to image ...[more]

PMID: 29746297

Similar Datasets

Project description:BACKGROUND:Despite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low-and-middle-income countries. High rates of loss to follow-up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow-up, improve virological suppression rates, and reduce mortality. OBJECTIVES:To assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies. SEARCH METHODS:We searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts. SELECTION CRITERIA:We included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta-analysis. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS:We included seven studies with 18,011 participants in the review. All studies were carried out in low- and middle-income countries in adults aged 18 years old or older. Only one study included pregnant women.In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART.Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate-certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate-certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low-certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low-certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low-certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events. AUTHORS' CONCLUSIONS:RCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low- and middle-income settings. The studies demonstrating these effects delivered rapid ART combined with several setting-specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems.

Project description:BackgroundLipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described.MethodsPlasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (n = 13) matched for age and sex.ResultsThe levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants (P < 0.01), and levels of these PUFAs were increased following 48 weeks of ART. Levels of PUFAs were often inversely related to immune activation. Levels of LPC were increased in HIV+ participants, both pre- and post-ART vs HIV- participants, and the composition of LPC was enriched for SaFAs among HIV+ individuals. At week 48, several LPC molecules containing SaFAs were positively correlated with levels of sCD14, D-dimer, and TNFR1 (P < 0.01), and levels of PUFA-containing LPC (18:3, 20:5, 22:5, 22:6) were positively correlated with CD4+ T cell counts and inversely correlated with sCD14 and IL-6 (P < 0.01).ConclusionsThe composition of the lipidome is altered in HIV infection and changes when ART is administered. Alterations in SaFAs were generally associated with inflammatory markers and may contribute to comorbid disease pathogenesis.

Dataset Information

Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy.

Publications

Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets