Understanding the use of co-design methods for research involving older adults living with HIV: A scoping review protocol.

There is a growing population of adults aged 50 years or older living with HIV, facing unique challenges in care due to age, minority status, and stigma. Co-design methodologies, aligning with patient-centered care, have potential for informing interventions addressing the complex needs of older adults with HIV. Despite challenges, co-design has shown promise in empowering older individuals to actively participate in shaping their care experiences. The scoping review outlined here aims to identify gaps in existing co-design work with this population, emphasizing the importance of inclusivity based on PROGRESS-Plus characteristics for future patient-oriented research. This scoping review protocol is informed by the Joanna Briggs Institute Manual to explore co-design methods in geriatric HIV care literature. The methodology encompasses six stages: 1) developing research questions, 2) creating a search strategy, 3) screening and selecting evidence, 4) data extraction, 5) data analysis using content analysis, and 6) consultation with key stakeholders, including community partners and individuals with lived experience. The review will involve a comprehensive literature search, including peer-reviewed databases and gray literature, to identify relevant studies conducted in the past 20 years. The inclusive criteria focus on empirical data related to co-design methods in HIV care for individuals aged 50 or older, aiming to inform future research and co-design studies in geriatric HIV care. The study will be limited by the exclusion of papers not published or translated to English. Additionally, the varied terminology used to describe co-design across different research may result in the exclusion of articles using alternative terms. The consultation with key stakeholders will be crucial for translating insights into meaningful co-design solutions for virtual HIV care, aiming to provide a comprehensive synthesis that informs evidence-based strategies and addresses disparities in geriatric HIV care.

Non-AIDS-defining comorbidities impact health related quality of life among older adults living with HIV.

Introduction: The life expectancy of people living with HIV receiving effective combination antiretroviral therapy is approaching that of the general population and non AIDS-defining age-related comorbidities are becoming of greater concern. In order to support healthy aging of this population, we set out to explore the association between multimorbidity (defined as presence of 2 or more non AIDS-defining comorbidities) and quality of life (QoL). Methods: We performed a cross-sectional analysis using data from the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV age 65 years and older. Study participants completed two QoL modules, the general QoL and health related QoL (HR-QoL). Results: 433 participants were included in the analysis with a median age of 69 years (interquartile range, IQR 67-72). The median number of comorbidities among study participants was 3 (IQR 2-4), with 78% meeting the definition of multimorbidity. General QoL scores (median 66, IQR 58-76) were lower than HR-QoL scores (median 71, IQR 61-83) and were not associated with multimorbidity after adjusting for age, sex, relationship status, household income, exercise, tobacco smoking history, malnutrition, time since HIV diagnosis, and HIV-related stigma. In contrast, multimorbidity was associated with lower HR-QoL (adjusted ß = -4.57, 95% CI -8.86, -0.28) after accounting for the same variables. Several social vulnerabilities (not having a partner, low household income), health behaviours (lower engagement in exercise, smoking), and HIV-related factors (HIV stigma, longer time since HIV diagnosis) were also associated with lower QoL. Discussion: Overall, our study demonstrated a high burden of multimorbidity among older adults living with HIV in Canada, which has a negative impact on HR-QoL. Interventions aimed at preventing and managing non-AIDS-defining comorbidities should be assessed in people living with HIV to determine whether this can improve their HR-QoL.

Exploring implementation considerations for geriatric-HIV clinics: A secondary analysis from a scoping review on HIV models of geriatric care.

OBJECTIVES: This review aimed to map the current state of knowledge regarding the implementation considerations of existing geriatric-HIV models of care, to identify areas of further research and to inform the implementation of future geriatric-HIV interventions that support older adults living with HIV. METHODS: We conducted a scoping review that was methodologically informed by the Arskey and O'Malley's 5 step framework and theoretically informed by the Consolidated Framework for Implementation Research (CFIR). A systematic search of six databases was conducted for peer-reviewed literature. The grey literature was also searched. Article screening was performed in duplicate. Data was extracted for the purpose of this secondary analysis using a data extraction template informed by the CFIR. Data was inductively and deductively analyzed. RESULTS: In total, 11 articles met the inclusion criteria. The models of care described varied in terms of their location and setting, the number and type of care providers involved, the mechanism of patient referral, the type of assessments and interventions performed and the methods of longitudinal patient follow-up. Four key categories emerged to describe factors that influenced their implementation: care provider buy-in, patient engagement, mechanisms of communication and collaboration, and available resources. CONCLUSIONS: The findings from this scoping review provide an initial understanding of the key factors to consider when implementing geriatric-HIV models of care. We recommend health system planners consider mechanisms of communication and collaboration, opportunities for care provider buy-in, patient engagement and available resources. Future research should explore implementation in more diverse settings to understand the nuances that influence implementation and care delivery.

Understanding geriatric models of care for older adults living with HIV: a scoping review and qualitative analysis.

BACKGROUND: Advances in Human Immunodeficiency Virus (HIV) treatment have reduced mortality rates and consequently increased the number of individuals with HIV living into older age. Despite this, people aged 50 years and older have been left behind in recent HIV treatment and prevention campaigns, and a gold-standard model of care for this population has not yet been defined. Developing evidence-based geriatric HIV models of care can support an accessible, equitable, and sustainable HIV health care system that ensures older adults have access to care that meets their needs now and in the future. METHODS: Guided by Arksey & O'Malley (2005)'s methodological framework, a scoping review was conducted to determine the key components of, identify gaps in the literature about, and provide recommendations for future research into geriatric models of care for individuals with HIV. Five databases and the grey literature were systematically searched. The titles, abstracts and full texts of the search results were screened independently in duplicate. Data were analyzed using a qualitative case study and key component analysis approach to identify necessary model components. RESULTS: 5702 studies underwent title and abstract screening, with 154 entering full-text review. 13 peer-reviewed and 0 grey literature sources were included. Most articles were from North America. We identified three primary model of care components that may improve the successful delivery of geriatric care to people living with HIV: Collaboration and Integration; Organization of Geriatric Care; and Support for Holistic Care. Most articles included some aspects of all three components. CONCLUSION: To provide effective geriatric care to older persons living with HIV, health services and systems are encouraged to use an evidence-based framework and should consider incorporating the distinct model of care characteristics that we have identified in the literature. However, there is limited data about models in developing countries and long-term care settings, and limited knowledge of the role of family, friends and peers in supporting the geriatric care of individuals living with HIV. Future evaluative research is encouraged to determine the impact of optimal components of geriatric models of care on patient outcomes.

Evaluating the use of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in the workup of Staphylococcus aureus bacteraemia: a cost-utility analysis.

OBJECTIVES: The use of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with Staphylococcus aureus bacteraemia can improve the diagnosis of infectious foci and guide clinical management. We aimed to evaluate the cost-utility of PET/CT among adults hospitalized with Staphylococcus aureus bacteraemia. METHODS: A cost-utility analysis was conducted from the healthcare payer perspective using a probabilistic Markov cohort model assessing three diagnostic strategies: (a) PET/CT in all patients, (b) PET/CT in high-risk patients only, and (c) routine diagnostic workup. Primary outcomes were quality-adjusted life years (QALYs), costs in Canadian dollars, and an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty. RESULTS: Routine workup resulted in an average of 16.64 QALYs from the time of diagnosis at a lifetime cost of $209 060/patient. This was dominated by PET/CT in high-risk patients (i.e. greater effectiveness at lower costs) with average 16.88 QALYs at a cost of $199 552. Compared with PET/CT in high-risk patients only, PET/CT for all patients cost on average $11 960 more but resulted in 0.14 more QALYs, giving an incremental cost-effectiveness ratio of $83 500 (cost per additional QALY gained); however, there was a high degree of uncertainty comparing these two strategies. At a willingness-to-pay threshold of $50 000/QALY, PET/CT in high-risk patients was the most cost-effective strategy in 58.6% of simulations vs. 37.9% for PET/CT in all patients. DISCUSSION: Our findings suggest that a strategy of using PET/CT in high-risk patients is more cost-effective than no PET/CT. Randomized controlled trials should be conducted to evaluate the use of PET/CT in different patient groups.

Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV)-CTN 314.

The Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, CTN 314, is the first Canadian cohort of people living with HIV aged 65 years and older. The cohort was established with the purpose of characterizing the multidimensional health status of this population and identifying factors influencing healthy aging. The study builds on the World Health Organization (WHO) Aging and Health conceptual framework, generating a comprehensive profile of health domains (physical, social, mental health, cognitive function, and quality of life), health determinants (biologic, personal, and environmental), and HIV-specific factors that may interact with and influence health in people aging with HIV. The data for the first 353 participants are presented, focusing on sociodemographic factors, comorbidities, coinfections, frailty, cognitive function, loneliness, and resilience using a sex/gender stratified analysis. The cohort thus far is 91% men and the median age is 70 years (range from 65 to 85). Several vulnerabilities were observed, including a high prevalence of comorbidities and frailty. Women especially faced financial insecurity and precarious social structures; a large proportion live alone and only 6% are married or in steady relationships. Identifying strategies to address these vulnerabilities will empower people aging with HIV to optimize their health, quality of life, and independence.

Diagnostic accuracy of subjective dyspnoea in detecting hypoxaemia among outpatients with COVID-19: a retrospective cohort study.

OBJECTIVES: The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnoea is challenging to assess remotely, and the accuracy of subjective dyspnoea measures in capturing hypoxaemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnoea in diagnosing hypoxaemia in COVID-19 patients. METHODS: This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from 3 April 2020 to 13 September 2020. Dyspnoea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV) and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxaemia. In the primary analysis, hypoxaemia was defined by oxygen saturation <95%; the diagnostic accuracy of subjective dyspnoea was also assessed across a range of oxygen saturation cutoffs from 92% to 97%. RESULTS: During the study period, 89/501 (17.8%) of patients met criteria for home oxygen saturation monitoring, and of these 17/89 (19.1%) were diagnosed with hypoxaemia. The presence/absence of dyspnoea had limited accuracy for diagnosing hypoxaemia, with SN 47% (95% CI 24% to 72%), SP 80% (95% CI 68% to 88%), NPV 86% (95% CI 75% to 93%), PPV 36% (95% CI 18% to 59%), +LR 2.4 (95% CI 1.2 to 4.7) and -LR 0.7 (95% CI 0.4 to 1.1). The SN of dyspnoea was 50% (95% CI 19% to 81%) when a cut-off of <92% was used to define hypoxaemia. A modified Medical Research Council dyspnoea score >1 (SP 98%, 95% CI 88% to 100%), Roth maximal count <12 (SP 100%, 95% CI 75% to 100%) and Roth counting time <8 s (SP 93%, 95% CI 66% to 100%) had high SP that could be used to rule in hypoxaemia, but displayed low SN (≤50%). CONCLUSIONS: Subjective dyspnoea measures have inadequate accuracy for ruling out hypoxaemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.

Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines.

OBJECTIVES: To determine the time to CD4 : CD8 ratio normalization among Canadian adults living with HIV in the modern ART era. To identify characteristics associated with ratio normalization. PATIENTS AND METHODS: Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan-Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization. RESULTS: Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62-0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11-0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5-1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization. CONCLUSIONS: Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used.

Association between initial symptoms and subsequent hospitalization in outpatients with COVID-19: A cohort study.

Background: Most individuals with coronavirus disease 2019 (COVID-19) experience mild symptoms and are managed in the outpatient setting. The aim of this study was to determine whether self-reported symptoms at the time of diagnosis can identify patients at risk of clinical deterioration. Methods: This was a retrospective cohort study of 671 outpatients with laboratory-confirmed COVID-19 diagnosed in Toronto between March 1 and October 16, 2020. We examined the association between patients' baseline characteristics and self-reported symptoms at the time of diagnosis and the risk of subsequent hospitalization. Results: Of 671 participants, 26 (3.9%) required hospitalization. Individuals aged 65 years or older were more likely to require hospitalization (odds ratio [OR] 5.29, 95% CI 2.19 to 12.77), whereas those without medical comorbidities were unlikely to be hospitalized (OR 0.02, 95% CI 0.00 to 0.17). After adjusting for age and presence of comorbidities, sputum production (adjusted OR [aOR] 5.01, 95% CI 1.97 to 12.75), arthralgias (aOR 4.82, 95% CI 1.85 to 12.53), diarrhea (aOR 4.56, 95% CI 1.82 to 11.42), fever (aOR 3.64, 95% CI 1.50 to 8.82), chills (aOR 3.62, 95% CI 1.54 to 8.50), and fatigue (aOR 2.59, 95% CI 1.04 to 6.47) were associated with subsequent hospitalization. Conclusions: Early assessment of symptoms among outpatients with COVID-19 can help identify individuals at risk of clinical deterioration. Additional studies are needed to determine whether more intense follow-up and early intervention among high-risk individuals can alter the clinical trajectory of and outcomes among outpatients with COVID-19.

Historique: La plupart des personnes atteintes de la maladie à coronavirus 2019 (COVID-19) éprouvent des symptômes légers et sont prises en charge en milieu ambulatoire. La présente étude visait à déterminer si les symptômes autodéclarés au moment du diagnostic permettent de dépister les patients à risque de détérioration clinique. Méthodologie: Les chercheurs ont réalisé la présente étude de cohorte rétrospective auprès de 671 patients ambulatoires atteints d'une COVID-19 diagnostiquée à Toronto et confirmée en laboratoire entre le 1er mars et le 16 octobre 2020. Ils ont examiné l'association entre les caractéristiques de référence et les symptômes autodéclarés des patients au moment du diagnostic, d'une part, et le risque d'hospitalisation, d'admission en soins intensifs ou de décès par la suite, d'autre part. Résultats: Des 671 participants, 26 (3,9 %) ont dû être hospitalisés, sept (1,0 %) ont été admis en soins intensifs et trois (0,4 %) sont décédés dans les 30 jours suivant le diagnostic. Les personnes de 65 ans ou plus étaient plus susceptibles de devoir être hospitalisées (RC 5,29, IC à 95 % 2,19 à 12,77) et celles qui n'avaient pas d'autres problèmes de santé l'étaient moins (RC 0,02, IC à 95 % 0,00 à 0,17). Après redressement pour tenir compte de l'âge et de la présence d'autres problèmes de santé, la production de mucus (RC ajusté [RCa] 5,01, IC à 95 % 2,11 à 13,66), les arthralgies (RCa 4,82, IC à 95 % 1,85 à 12,53), la diarrhée (RCa 4,56, IC à 95 % 1,82 à 11,42), la fièvre (RCa 3,64, IC à 95 % 1,50 à 8,82), les frissons (RCa 3,62, IC à 95 % 1,54 à 8,50) et la fatigue (RCa 2,59, IC à 95 % 1,04 à 6,47) étaient associés à des hospitalisations. Conclusions: L'évaluation précoce des symptômes des patients ambulatoires atteints de la COVID-19 peut contribuer à dépister les personnes vulnérables à une détérioration clinique. Lorsque ce facteur s'ajoute à l'âge et à l'histoire de problèmes de santé, la symptomatologie fournit plus d'information pronostique aux cliniciens qui prennent en charge les patients atteints de COVID-19 en milieu ambulatoire. D'autres études s'imposent pour déterminer si un suivi plus intense et une intervention précoce auprès des personnes très vulnérables peuvent modifier la trajectoire clinique et le pronostic des patients ambulatoires atteints de la COVID-19.

Barriers to HIV pre-exposure prophylaxis among African, Caribbean and Black men in Toronto, Canada.

INTRODUCTION: Single-tablet combination emtricitabine/tenofovir is highly effective as HIV pre-exposure prophylaxis (PrEP). Scale-up efforts have targeted men who have sex with men (MSM), but patterns of racial disparities in PrEP use have begun to emerge. African, Caribbean and Black (ACB) communities in Canada and USA are also disproportionately affected by HIV, and there is lack of guidance regarding PrEP implementation in this priority population. METHODS: ACB men from Toronto, Canada were recruited in community settings by peers. Participants completed a detailed socio-behavioural questionnaire. Biological samples were collected and tested for sexually transmitted infections. Willingness to accept PrEP was assessed in relation to actual and self-perceived risk of acquiring HIV, as well as demographic and behavioural variables. RESULTS: 424 ACB men were included in the analysis. ACB MSM were more likely to accept PrEP than ACB men only reporting sex with women (MSW; 50.0% vs. 23.6%). The most common reasons for PrEP non-acceptance were concerns regarding side-effects and low self-perceived risk. PrEP acceptance was lowest among younger men (12.5%) and those born in Canada (15.2%). Men with a high self-perceived HIV risk were more likely to accept PrEP (41.3% vs. 22.7% of men with a low self-perceived risk), but only 25.4% of men who were defined as being at high-risk, self-identified themselves as such. CONCLUSIONS: Most ACB MSW were unlikely to accept PrEP, largely due to low self-perceived HIV risk, but PrEP acceptance among ACB MSM was similar to other contemporaneous Toronto MSM communities. PrEP acceptance was particularly low among younger ACB men and those born in Canada. Tailored strategies will be needed to effectively implement PrEP in Toronto ACB communities.

Pokeweed antiviral protein alters splicing of HIV-1 RNAs, resulting in reduced virus production.

Processing of HIV-1 transcripts results in three populations in the cytoplasm of infected cells: full-length RNA, singly spliced, and multiply spliced RNAs. Rev, regulator of virion expression, is an essential regulatory protein of HIV-1 required for transporting unspliced and singly spliced viral transcripts from the nucleus to the cytoplasm. Export allows these RNAs to be translated and the full-length RNA to be packaged into virus particles. In our study, we investigate the activity of pokeweed antiviral protein (PAP), a glycosidase isolated from the pokeweed plant Phytolacca americana, on the processing of viral RNAs. We show that coexpression of PAP with a proviral clone alters the splicing ratio of HIV-1 RNAs. Specifically, PAP causes the accumulation of multiply spliced 2-kb RNAs at the expense of full-length 9-kb and singly spliced 4-kb RNAs. The change in splicing ratio is due to a decrease in activity of Rev. We show that PAP depurinates the rev open reading frame and that this damage to the viral RNA inhibits its translation. By decreasing Rev expression, PAP indirectly reduces the availability of full-length 9-kb RNA for packaging and translation of the encoded structural proteins required for synthesis of viral particles. The decline we observe in virus protein expression is not due to cellular toxicity as PAP did not diminish translation rate. Our results describing the reduced activity of a regulatory protein of HIV-1, with resulting change in virus mRNA ratios, provides new insight into the antiviral mechanism of PAP.

RNA toxins: mediators of stress adaptation and pathogen defense.

RNA toxins are a group of enzymes primarily synthesized by bacteria, fungi, and plants that either cleave or depurinate RNA molecules. These proteins may be divided according to their RNA substrates: ribotoxins are nucleases that cleave ribosomal RNA (rRNA), ribosome inactivating proteins are glycosidases that remove a base from rRNA, messenger RNA (mRNA) interferases are nucleases that cleave mRNAs, and anticodon nucleases cleave transfer RNAs (tRNAs). These modifications to the RNAs may substantially alter gene expression and translation rates. Given that some of these enzymes cause cell death, it has been suggested that they function mainly in defense, either to kill competing cells or to elicit suicide and thereby limit pathogen spread from infected cells. Although good correlations have been drawn between their enzymatic functions and toxicity, recent work has shown that some RNA toxins cause apoptosis in the absence of damage to RNA and that defense against pathogens can be achieved without host cell death. Moreover, a decrease in cellular translation rate, insufficient to cause cell death, allows some organisms to adapt to stress and environmental change. Although ascribing effects observed in vitro to the roles of these toxins in nature has been challenging, recent results have expanded our understanding of their modes of action, and emphasized the importance of these toxins in development, adaptation to stress and defense against pathogens.