Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS ...opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV.
Abstract
As care of persons living with human immunodeficiency virus (HIV; PWH) has transitioned from management of opportunistic infections to management of conditions associated with older age, new ...models of geriatric consultation are needed. The authors, who represent 9 clinics across North America and the United Kingdom, provided their insights on models of geriatric consultation for older PWH. Three models of geriatric consultation are delineated: outpatient referral/consultation, combined HIV/geriatric multidisciplinary clinic, and dually trained providers within 1 clinical setting. A patient-centered approach and the use of expertise across disciplines were universally identified as strengths. Logistical barriers and the reluctance of older PWH to see a geriatric care provider were identified as barriers to implementing these models. Although the optimal model of geriatric consultation depends on a region’s resources, there is value in augmenting the training of infectious disease providers to include principles of geriatric care.
For persons with human immunodeficiency virus (HIV) age 50 and over, there is an increasing need to address concerns associated with aging. Three models of geriatric consultation are described: outpatient referral/consultation, combined HIV/geriatric multidisciplinary clinic, and dually trained providers.
Background: In Japan, most new HIV cases are reported amongst men who have sex with men (MSM); thus, there is an urgent need for further widespread testing of MSM. The use of Digital Vending Machines ...(DVM) in the UK offering HIV test kits targeting MSM show promising results. Digital Vending Machines could be useful to promote and increase the uptake of testing in Japan, although no studies have yet been conducted. We aimed to assess the acceptability and feasibility of distributing HIV test kits using DVMs exploring needs and concerns as well as preferred types of test kits and locations.
Methods: Fifty-four individuals participated in workshops and meetings with a further 224 MSM answering a quantitative survey assessing HIV testing and prevention needs.
Results: Amongst MSM who had never been tested, 73% showed willingness to purchase tests from DVMs. Responses were broadly positive about DVMs but there were concerns regarding being seen receiving test kits from the machines and linkage to confirmatory testing and appropriate care.
Conclusions: Using DVMs to distribute HIV test kits in Japan was found to be both acceptable and feasible and may have the potential to increase access to testing for MSM. Future large-scale evaluation studies are required.
People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. In the general population, depression is associated with peripheral and central ...inflammation. Given this, and since HIV infection elicits inflammation, we hypothesised that peripheral and central inflammatory biomarkers would at least partly mediate the association between HIV and depressive symptoms. People living with HIV (n = 125) and without HIV (n = 79) from the COmorBidity in Relation to AIDS (COBRA) cohort were included in this study. Participants living with and without HIV had similar baseline characteristics. All participants living with HIV were on antiretroviral therapy and were virally suppressed. Plasma, CSF, and brain MR spectroscopy (MRS) biomarkers were measured. Using logistic regression models adjusted for sociodemographic factors, we found that participants with HIV were more likely to have Any Depressive Symptoms (Patient Health Questionnaire PHQ-9 score >4) (odds ratio 95% confidence interval 3.27 1.46, 8.09). We then sequentially adjusted the models for each biomarker separately to determine the mediating role of each biomarker, with a >10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (-15.0%) and TNF-α (-11.4%) in plasma and MIP1-α (-21.0%) and IL-6 (-18.0%) in CSF mediated the association between HIV and depressive symptoms in this sample. None of the other soluble or neuroimaging biomarkers substantially mediated this association. Our findings suggest that certain biomarkers of central and peripheral inflammation may at least partly mediate the relationship between HIV and depressive symptoms.
Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. The 2007 criteria for HIV-associated ...neurocognitive disorders (HAND), sometimes called the Frascati criteria, can falsely classify over 20% of cognitively healthy individuals as having cognitive impairment. Minimum criteria for HAND are met on the basis of performance on cognitive tests alone, which might not be appropriate for populations with diverse educational and socioeconomic backgrounds. Imprecise phenotyping of cognitive impairment can limit mechanistic research, biomarker discovery and treatment trials. Importantly, overestimation of cognitive impairment carries the risk of creating fear among people living with HIV and worsening stigma and discrimination towards these individuals. To address this issue, we established the International HIV-Cognition Working Group, which is globally representative and involves the community of people living with HIV. We reached consensus on six recommendations towards a new approach for diagnosis and classification of cognitive impairment in people living with HIV, intended to focus discussion and debate going forward. We propose the conceptual separation of HIV-associated brain injury - including active or pretreatment legacy damage - from other causes of brain injury occurring in people living with HIV. We suggest moving away from a quantitative neuropsychological approach towards an emphasis on clinical context. Our recommendations are intended to better represent the changing profile of cognitive impairment in people living with HIV in diverse global settings and to provide a clearer framework of classification for clinical management and research studies.
Prompt HIV and STI diagnosis and treatment is a public health priority and relies on accessible testing. Technology-based approaches to distribute test kits have the potential to increase access to ...testing. We evaluated the acceptability and uptake of vending machines in publicly available settings in Brighton and Hove (BH) and Bristol, North Somerset and South Gloucestershire (BNSSG), to distribute HIV rapid self-test and STI self-sample kits.
Seven machines were installed in BH and four in BNSSG. User characteristics, proportion of kits returned and test results, taken from the machine database and clinic records, combined with online questionnaires completed by self-recruited users and analysed using Stata and SPSS.
2536 kits were dispensed over 12 months (April 2022 to March 2023). The STI self-sample kits were most popular (74% of vends). 78% of kits dispensed were among users aged 16-35 years and 56% identified as male. 68% and 59% of users had either not tested in the last 12 months or never tested for HIV and STIs, respectively. 51% of STI kits were returned via post, lower than the local online service (65%). 208 users completed questionnaires. Convenience, desire for instant access and increased confidentiality were the most common reasons for using machines. 92% of respondents thought the machines were user-friendly and 97% would recommend the service. Concerns about safety and privacy while using the machine were reported by 42% and 66% of respondents.
This study demonstrates that vending machines are an acceptable and effective means of accessing infrequent or never testers in the general population and can act as a horizontal intervention to tackle HIV and STIs. Research is needed to understand optimal machine locations to assure privacy and safety along with the long-term impact on sexual health services.
IntroductionAs the prevalence of Long COVID increases, there is a critical need for a comprehensive assessment of disability. Our aims are to: (1) characterise disability experiences among people ...living with Long COVID in Canada, UK, USA and Ireland; and (2) develop a patient-reported outcome measure to assess the presence, severity and episodic nature of disability with Long COVID.Methods and analysisIn phase 1, we will conduct semistructured interviews with adults living with Long COVID to explore experiences of disability (dimensions, uncertainty, trajectories, influencing contextual factors) and establish an episodic disability (ED) framework in the context of Long COVID (n~10 each country). Using the conceptual framework, we will establish the Long COVID Episodic Disability Questionnaire (EDQ). In phase 2, we will examine the validity (construct, structural) and reliability (internal consistency, test–retest) of the EDQ for use in Long COVID. We will electronically administer the EDQ and four health status criterion measures with adults living with Long COVID, and readminister the EDQ 1 week later (n~170 each country). We will use Rasch analysis to refine the EDQ, and confirm structural and cross-cultural validity. We will calculate Cronbach’s alphas (internal consistency reliability), and intraclass correlation coefficients (test–retest reliability), and examine correlations for hypotheses theorising relationships between EDQ and criterion measure scores (construct validity). Using phase 2 data, we will characterise the profile of disability using structural equation modelling techniques to examine relationships between dimensions of disability and the influence of intrinsic and extrinsic contextual factors. This research involves an academic–clinical–community partnership building on foundational work in ED measurement, Long COVID and rehabilitation.Ethics and disseminationThis study was approved by the University of Toronto Research Ethics Board. Knowledge translation will occur with community collaborators in the form of presentations and publications in open access peer-reviewed journals and presentations.
Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, ...using translocator protein (TSPO)
CPBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent
CPBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (V
) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in V
and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in V
and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean V
compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using
CPBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute
CPBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.
The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of ...the Episodic Disability Questionnaire (EDQ) with adults living with HIV.
We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity).
Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed.
The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.
People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk.
We assessed thirty-one biomarkers in a subset ...of POPPY participants and identified three distinct inflammatory profiles: 'gut/immune activation', 'neurovascular', and 'reference' (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression.
Of the 312 participants included 70% living with HIV, median (interquartile range; IQR) age 55 (51-60) years; 82% male; 91% white, 36, 130, and 146 were in the 'gut/immune activation', 'neurovascular', and 'reference' cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5-14.5) and 10.2% (5.5-16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK 5.8% (1.0-10.7) and 3.1% (0.3-5.8) scores were higher, respectively, for those in the 'gut/immune activation' and 'neurovascular' clusters compared to those in the reference cluster.
People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV.
PDF
