Dataset Information

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.

ABSTRACT: Inflammation in people living with HIV (PLWH) correlates with severity of HIV-associated neurocognitive disorders. The objective of this study is to identify blood-based markers of neurocognitive function in a demographic balanced cohort of PLWH. Seven neurocognitive domains were evaluated in 121 seropositive Black/African American, Non-Hispanic White, and White Hispanic men and women using computerized assessments. Associations among standardized neurocognitive function and HIV-related parameters, relevant sociodemographic variables, and inflammation-associated cytokines measured in plasma and cellular supernatants were examined using multivariate and univariate regression models. Outlier and covariate analyses were used to identify and normalize for education level, CD4 T cell count, viral load, CNS and drug abuse comorbidities, which could influence biomarker and neurocognitive function associations. Plasma levels of chemokine (C-C motif) ligand (CCL) 8 significantly associated with memory, complex attention, cognitive flexibility, psychomotor speed, executive function, and processing speed. Plasma tissue inhibitor of metalloproteinases 1 associated with the aforementioned domains except memory and processing speed. In addition, plasma interleukin-23 significantly associated with processing speed and executive function. Analysis of peripheral blood cell culture supernatants revealed no significant markers for neurocognitive function. In this cohort, CD4 T cell count and education level also significantly associated with neurocognitive function. All identified inflammatory biomarkers demonstrated a negative correlation to neurocognitive function. These cytokines have known connections to HIV pathophysiology and are potential biomarkers for neurocognitive function in PLWH with promising clinical applications.

SUBMITTER: Swanta N

PROVIDER: S-EPMC7332393 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV-) participants as a comparison group. At two time points, messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV- adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the Illumina HT-12 v4 Expression BeadChip. All participants received baseline and follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed using standard gene expression analysis and weighted gene co-expression network analysis with correction for multiple testing. Gene sets were analyzed for GO term enrichment. Only weak reproducibility of associations of single genes with neurocognitive functioning was observed, indicating that such measures are unreliable as biomarkers for HIV-related NCI; however, gene networks were generally preserved between time points and largely reproducible, suggesting that these may be more reliable. Several gene networks associated with variables related to HIV infection were found (e.g., MHC I antigen processing, TNF signaling, interferon gamma signaling, and antiviral defense); however, no significant associations were found for neurocognitive function. Furthermore, neither individual gene probes nor gene networks predicted later neurocognitive change. This study did not validate our previous findings and does not support the use of monocyte gene expression profiles as a biomarker for current or future HIV-associated neurocognitive impairment.

Project description:IntroductionCurrent tuberculosis triage and predictive tools offer poor accuracy and are ineffective for detecting asymptomatic disease in people living with HIV (PLHIV). Host tuberculosis transcriptomic biomarkers hold promise for diagnosing prevalent and predicting progression to incident tuberculosis and guiding further investigation, preventive therapy and follow-up. We aim to conduct a systematic review of performance of transcriptomic signatures of tuberculosis in PLHIV.Methods and analysisWe will search MEDLINE (PubMed), WOS Core Collection, Biological Abstracts, and SciELO Citation Index (Web of Science), Africa-Wide Information and General Science Abstracts (EBSCOhost), Scopus, and Cochrane Central Register of Controlled Trials databases for articles published in English between 1990 and 2020. Case-control, cross-sectional, cohort and randomised controlled studies evaluating performance of diagnostic and prognostic host-response transcriptomic signatures in PLHIV of all ages and settings will be included. Eligible studies will include PLHIV in signature test or validation cohorts, and use microbiological, clinical, or composite reference standards for pulmonary or extrapulmonary tuberculosis diagnosis. Study quality will be evaluated using the 'Quality Assessment of Diagnostic Accuracy Studies-2' tool and cumulative review evidence assessed using the 'Grading of Recommendations Assessment, Development and Evaluation' approach. Study selection, quality appraisal and data extraction will be performed independently by two reviewers. Study, cohort and signature characteristics of included studies will be tabulated, and a narrative synthesis of findings presented. Primary outcomes of interest, biomarker sensitivity and specificity with estimate precision, will be summarised in forest plots. Expected heterogeneity in signature characteristics, study settings, and study designs precludes meta-analysis and pooling of results. Review reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines.Ethics and disseminationFormal ethics approval is not required as primary human participant data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentation.Prospero registration numberCRD42021224155.

Project description:BackgroundChronic HIV infection significantly elevates the risk of brain pathology, precipitating neurocognitive impairment (NCI) among people living with HIV (PLWH). The diagnosis of NCI in PLWH hinges on evaluating deviations in neuropsychological test performance in comparison to HIV-seronegative normative controls. However, the adverse psychosocial conditions experienced by PLWH can also result in reduced test performance, potentially confounding the accurate NCI attribution to HIV infection. This planned systematic review aims to investigate potential disparities in the excess burden of NCI among PLWH in two groups of studies: (a) studies enrolling controls who shared a similar mode of HIV exposure (MoHE) with the PLWH participants (MoHE-adjusted) and (b) studies enrolling normative controls or controls without undefined MoHE (MoHE-naive).MethodsWe will systematically search five electronic databases (MEDLINE, Embase, PsycINFO, Web of Science, ProQuest) and registries (OpenGrey, ClinicalTrials.gov, ISRCTN registry). Studies reporting NCI in PLWH and HIV-seronegative controls with cross-sectional or baseline measurements, published from January 2007 to September 2023, will be included. To be classified as MoHE adjusted, a study must evidence ≥ 90% enrolment of both PLWH and their seronegative controls from the same MoHE group (e.g. men who have sex with men, people who use drugs or alcohol). Reports of test performance scores will be transformed into NCI proportions using simulated score distributions, applying a global deficit score cut-off ≥ 0.5 to estimate NCI cases. The Newcastle-Ottawa scale adapted to the purpose of the review will be used to appraise study quality. Random-effects meta-analysis will be used to pool the excess burden of NCI in prevalence ratios and test the difference between MoHE-adjusted and MoHE-naive studies. Furthermore, subgroup analyses and meta-regression will be undertaken across categorical study-level covariates (e.g. study locations, NCI diagnostic criteria) and continuous/ordinal covariates (nadir CD4, number of neurocognitive domains assessed), respectively.DiscussionThis systematic review will contribute towards a greater appreciation of the unique psychosocial conditions of PLWH that are missing from the current case definition of HIV-associated neurocognitive disorder. The findings will additionally highlight possible disparities in the distribution of the excess burden of NCI by MoHE groups, thereby guiding the prioritization of mitigation efforts.Systematic review registrationPROSPERO CRD42021271358.

Project description:Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to - 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline.Trial registration: NCT00867048 and NCT01797367.

Dataset Information

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets