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.

Ageism: the -ism affecting the lives of older people living with HIV.

WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV.

Baseline characteristics of a prospective cohort study of aging and cardiovascular diseases among people living with HIV.

OBJECTIVES: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. METHODS: CHACS is a multi-centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow-up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender-gender roles, gender identity, gender relationships, and institutionalized gender-will be measured using the GENESIS-PRAXY questionnaire. Diet will be assessed using a validated, web-based, self-administered food frequency questionnaire. RESULTS: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50-61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. CONCLUSIONS: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio-economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.

Practical management of complexity in older people with HIV: approaching an international consensus.

ABSTRACTGlobally the community of people with HIV is ageing, and some of these have increasingly complex care needs, with a known excess of non-HIV related comorbidities and related issues including consequent polypharmacy. At the 2022 International AIDS Conference in Montréal, Canada, the "Silver Zone" was created in the Global Village as a safe space for older people with HIV. As part of the Silver Zone activities, a session discussing global models of care for in this group was held. HIV treatment providers and advocates from diverse resource settings and with a diversity of expertise were invited to share their experience, reflections, and ideas, and this consensus statement was formed based on these discussions. Different approaches to care emerged, based on local needs and resources, and it became clear that issues of complexity and frailty need not be age limited. Despite clear regional differences, some common themes became apparent, and a consensus was established on basic principles that may be considered in diverse settings. These are discussed here, with agreement on necessary proximal steps to develop bespoke person-centred care models.

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.

The Relationship between Visceral Adiposity and Nonalcoholic Fatty Liver Disease Diagnosed by Controlled Attenuation Parameter in People with HIV: A Pilot Study.

Background: Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral adiposity in PWH. Methods: We conducted a prospective pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP measured by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥ 285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT > 1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Results: Thirty patients were included, of whom 50% had NAFLD. CAP was correlated with VAT (r = 0.650, p < 0.001) measured by DEXA scan. After adjusting for duration of HIV infection, body mass index and waist circumference, CAP remained the only independent predictor of excess VAT (adjusted odds ratio 1.05, 95% confidence interval [CI] 1.01−1.10). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81−1.00), higher than BMI and waist circumference. The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. Conclusions: NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP may be a potential diagnostic marker of visceral adiposity in the practice of HIV medicine.

Frailty in older people living with HIV: current status and clinical management.

This paper will update care providers on the clinical and scientific aspects of frailty which affects an increasing proportion of older people living with HIV (PLWH). The successful use of combination antiretroviral therapy has improved long-term survival in PLWH. This has increased the proportion of PLWH older than 50 to more than 50% of the HIV population. Concurrently, there has been an increase in the premature development of age-related comorbidities as well as geriatric syndromes, especially frailty, which affects an important minority of older PLWH. As the number of frail older PLWH increases, this will have an important impact on their health care delivery. Frailty negatively affects a PLWH's clinical status, and increases their risk of adverse outcomes, impacting quality of life and health-span. The biologic constructs underlying the development of frailty integrate interrelated pathways which are affected by the process of aging and those factors which accelerate aging. The negative impact of sarcopenia in maintaining musculoskeletal integrity and thereby functional status may represent a bidirectional interaction with frailty in PLWH. Furthermore, there is a growing body of literature that frailty states may be transitional. The recognition and management of related risk factors will help to mitigate the development of frailty. The application of interdisciplinary geriatric management principles to the care of older PLWH allows reliable screening and care practices for frailty. Insight into frailty, increasingly recognized as an important marker of biologic age, will help to understand the diversity of clinical status occurring in PLWH, which therefore represents a fundamentally new and important aspect to be evaluated in their health care.

Strengths and Challenges of Various Models of Geriatric Consultation for Older Adults Living With Human Immunodeficiency Virus.

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.

Characterization of people living with HIV in a Montreal-based tertiary care center with COVID-19 during the first wave of the pandemic.

People living with HIV (PLWH) often have worse health outcomes compared to HIV-uninfected individuals. We characterized PLWH followed at a tertiary care clinic in Montreal who acquired COVID-19 and described their outcomes during the first wave of the pandemic. A retrospective chart review was performed for PLWH followed at the Chronic Viral Illness Service with a positive COVID-19 nasopharyngeal PCR or symptoms suggestive of COVID-19 between 1 March and 15 June 2020. Data on demographics, socioeconomic status, co-morbidities and severity of COVID-19 and outcomes were extracted. Of 1702 individuals, 32 (1.9%) had a positive COVID-19 test (n = 24) or symptoms suspicious for COVID-19 (n = 3). Median age was 52 years [IQR 40, 62]. Nearly all (97%) earned $34,999 Canadian dollars or less. Eleven (34%) individuals worked in long-term care (LTC) homes while 5 (6%) lived in LTC homes. Median CD4 count was 566 cells/mm3 [347, 726] and six had detectable plasma HIV viral loads. Median duration of HIV was 17 years [7, 22] and 30 individuals had been prescribed antiretroviral therapy. Five persons were asymptomatic. Of symptomatic persons, 21 (12%), 1 (4%) and 3 (12%) individuals had mild, moderate and severe disease, respectively. Three individuals died with COVID-19. In one case, the cause of death was due to COVID-19, whereas in the other two cases, the individuals died with positive COVID-19 test results but the immediate cause of death is unclear. PLWH who tested positive for COVID-19 had low socioeconomic status and had employment or living conditions that put them at high risk. PLWH may be disproportionately impacted by the social determinants of health which predispose them to COVID-19.

Frailty: the current challenge for aging people with HIV.

PURPOSE OF REVIEW: Older adults account for the majority of people with HIV (PWH) in high-income countries and have increasingly complex clinical profiles related to premature aging. Frailty is an important geriatric syndrome affecting a minority of PHW. Frailty negatively affects PHW's clinical status and quality of life. This review will update care providers on the current state of frailty that limits the healthspan of PWH. RECENT FINDINGS: Ongoing low-level HIV replication in treated PWH leads to immune activation and chronic inflammation contributing to the destabilization of normally autoregulated physiologic systems in response to environmental and biologic challenges characteristic of frailty. Understanding these underlying mechanisms will determine potential intervention options. Potentially reversible risk factors that promote progression to and reversion from the dynamic state of frailty are being studied and will help prevent frailty. Simple assessment tools and treatment strategies for frailty are being adapted for aging PWH. SUMMARY: Insight into underlying biologic mechanisms and adapting proven geriatric principles of interdisciplinary care will inform the healthy aging of PWH.

Tesamorelin improves fat quality independent of changes in fat quantity.

OBJECTIVES: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density. DESIGN: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader. RESULTS: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5-7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3-4.7), P < 0.001] area change. CONCLUSION: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group.

Geriatric Syndromes in People Living with HIV Associated with Ageing and Increasing Comorbidities: Implications for Neurocognitive Complications of HIV Infection.

Long-term survival of treated people living with HIV (PLWH) currently approaches that of the general population. The average age of PLWH is currently in the mid-50s in resource-rich countries and is predicted that over 40% of PLWH will be older than 60 within a decade. Similar trends have been confirmed in all communities of PLWH with access to antiretroviral therapies. However, the positive impact on survival has been challenged by several developments. Ageing PLWH have clinical features similar to the general population about 5-10 years older. In addition to the earlier occurrence of common age-related conditions common geriatric syndromes have also impacted this population prematurely. These are often difficult to evaluate and manage conditions usually of multifactorial aetiology. They include polypharmacy, frailty, impaired mobility and falls, sarcopenia, sensory impairment, and increasingly, non-dementing cognitive decline. Cognitive decline is of particular concern to PLWH and their care providers. In the general geriatric population cognitive impairment increases with age and occurs in all populations with a prevalence of over 25% in people over 80. Effective treatments are lacking and therefore minimizing risk factors plays an important role in maintaining healthspan. In the general population geriatric syndromes may increase the risk of cognitive decline. The corollary is that decreasing the risk of their development may limit cognitive impairment. Whether a similar status holds in PLWH is uncertain. This chapter will address the question of whether common geriatric syndromes in PLWH contribute to cognitive impairment. Common risk factors may provide clues to limit or delay cognitive decline.

Author Correction: HIV and antiretroviral therapy-related fat alterations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

HIV and antiretroviral therapy-related fat alterations.

Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss (lipoatrophy), with or without central fat accumulation (lipohypertrophy), was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy. The subsequent identification of thymidine analogue nucleoside reverse transcriptase inhibitors as the cause of lipoatrophy led to the development of newer antiretroviral agents; however, studies have demonstrated continued abnormalities in fat and/or lipid storage in PLWH treated with newer drugs (including integrase inhibitor-based regimens), with fat gain due to restoration to health in antiretroviral therapy-naive PLWH, which is compounded by the rising rates of obesity. The mechanisms of fat alterations in PLWH are complex, multifactorial and not fully understood, although they are known to result in part from the direct effects of HIV proteins and antiretroviral agents on adipocyte health, genetic factors, increased microbial translocation, changes in the adaptive immune milieu after infection, increased tissue inflammation and accelerated fibrosis. Management includes classical lifestyle alterations with a role for pharmacological therapies and surgery in some patients. Continued fat alterations in PLWH will have an important effect on lifespan, healthspan and quality of life as patients age worldwide, highlighting the need to investigate the critical uncertainties regarding pathophysiology, risk factors and management.

Frailty in People Living with HIV.

PURPOSE OF REVIEW: Different factors contribute to the decreased overall long-term survival in treated people living with HIV (PLWH). This paper will review the state of physical frailty which limits successful aging in PLWH. RECENT FINDINGS: Identifiable events on the continuum from clinical normality to heightened risk of adverse health outcomes contribute to frailty. These center on chronic inflammation leading to destabilization of autoregulated physiologic systems challenged by environmental and biologic challenges. Frailty assessment can inform the profile of aging PLWH at increased risk of common age-related disorders and geriatric syndromes. Biologic and psychosocial risk factors promoting progression to and reversion from a dynamic state of frailty are being investigated, allowing for preventative interventions to be considered. Insights gained from studying frail PLWH will help adapt an interdisciplinary geriatric model of health care for selected PLWH. This will improve the health and well-being of aging PLWH.

Nonalcoholic Fatty Liver Disease and the Development of Metabolic Comorbid Conditions in Patients With Human Immunodeficiency Virus Infection.

BACKGROUND: Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH. METHODS: We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards. RESULTS: The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5-50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09-7.27] vs 0.87 [.42-1.83] per 100 person-years) and dyslipidemia (8.16 [5.42-12.27] vs 3.99 [2.67-5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14-12.31) and dyslipidemia (2.35; 1.34-4.14) development. CONCLUSIONS: HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.

The Interplay Between Age and Frailty in People Living With HIV: Results From an 11-Year Follow-up Observational Study.

Between 2006 and 2017, frailty prevalence decreased in HIV-positive individuals aged 50 years but presented a 3-fold increase among those 75 years of age. This dynamic relationship, defined as the frailty compression ratio, represents the net result of gero-inducing and gero-protective competing forces, described in the cohort.

Lean mass declines consistently over 10 years in people living with HIV on antiretroviral therapy, with patterns differing by sex.

BACKGROUND: The long-term trajectory of and factors affecting lean mass in people living with HIV (PLWH) are incompletely described. METHODS: PLWH in the Modena HIV Metabolic Cohort underwent dual-energy X-ray absorptiometry (DXA) scans every 6-12 months for up to 10 years (median 4.6 scans). Mixed effect regression modelling in combined and sex-stratified models determined annual rates of and clinical factors significantly associated with appendicular lean mass (ALM). RESULTS: A total of 839 women and 1,759 men contributing ≥2 DXA scans had baseline median age 44 years and 14 years since HIV diagnosis; 76% were virologically suppressed on antiretroviral therapy (ART). Baseline median ALM was 16.9 kg for women and 24.8 kg for men. ALM decreased during the study period, with mean yearly ALM loss of -231 g in women and -322 g in men. Less ALM was associated with female sex, age >50 years, detectable HIV-1 RNA, and tenofovir and integrase inhibitor use. Greater ALM was associated with longer ART duration. In sex-stratified models, relationships between ALM and total ART duration and integrase inhibitor use were not significant for women, but the relationship with tenofovir use persisted. For men, AIDS wasting and CD4+ T-lymphocyte nadir <200 cells/µl were independently associated with lower ALM. CONCLUSIONS: ALM steadily declined over time in this cohort of PLWH on ART that included a large number of women. HIV- and ART-specific risk factors emerged that varied by sex. The observed associations between tenofovir or integrase inhibitor use and lower ALM particularly warrant further study.