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Background and Aims: Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections., Methods: We searched PubMed, EMBASE, Scopus, CINAHL and PsycINFO from 1 January 2000 to 18 February 2021. Informed by Rhodes' 'risk environment' framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; and (3) consolidating descriptive themes into conceptual categories to identify higher-order analytical themes., Results: We screened 4841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytical themes. The first analytical theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health-care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programmes, including structural barriers to effective service provision. The second analytical theme, practices of care among people who use drugs, addressed protective strategies that people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g. HIV transmission)., Conclusions: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services and harmful health-care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Introduction: Injecting-related bacterial and fungal infections are a common complication among people who inject drugs (PWID), associated with significant morbidity and mortality. Invasive infections, including infective endocarditis, appear to be increasing in incidence. To date, preventive efforts have focused on modifying individual-level risk behaviours (eg, hand-washing and skin-cleaning) without much success in reducing the population-level impact of these infections. Learning from successes in HIV prevention, there may be great value in looking beyond individual-level risk behaviours to the social determinants of health. Specifically, the risk environment conceptual framework identifies how social, physical, economic and political environmental factors facilitate and constrain individual behaviour, and therefore influence health outcomes. Understanding the social and structural determinants of injecting-related bacterial and fungal infections could help to identify new targets for prevention efforts in the face of increasing incidence of severe disease., Methods and Analysis: This is a protocol for a systematic review. We will review studies of PWID and investigate associations between risk factors (both individual-level and social/structural-level) and the incidence of hospitalisation or death due to injecting-related bacterial infections (skin and soft-tissue infections, bacteraemia, infective endocarditis, osteomyelitis, septic arthritis, epidural abscess and others). We will include quantitative, qualitative and mixed methods studies. Using directed content analysis, we will code risk factors for these infection-related outcomes according to their contributions to the risk environment in type (social, physical, economic or political) and level (microenvironmental or macroenvironmental). We will also code and present risk factors at each stage in the process of drug acquisition, preparation, injection, superficial infection care, severe infection care or hospitalisation, and outcomes after infection or hospital discharge., Ethics and Dissemination: As an analysis of the published literature, no ethics approval is required. The findings will inform a research agenda to develop and implement social/structural interventions aimed at reducing the burden of disease., Prospero Registration Number: CRD42021231411., Competing Interests: Competing interests: MB reports personal fees from AbbVie, a pharmaceutical research and development company, and grants and personal fees from Gilead Sciences, a research-based biopharmaceutical company, outside of the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

People who use drugs (PWUD) face concurrent public health emergencies from overdoses, HIV, hepatitis C, and COVID-19, leading to an unprecedented syndemic. Responses to PWUD that go beyond treatment--such as decriminalization and providing a safe supply of pharmaceutical-grade drugs--could reduce impacts of this syndemic. Solutions already implemented for COVID-19, such as emergency safe-supply prescribing and providing housing to people experiencing homelessness, must be sustained once COVID-19 is contained. This pandemic is not only a public health crisis but also a chance to develop and maintain equitable and sustainable solutions to the harms associated with the criminalization of drug use.

Objectives: Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV., Methods: This was a cross-sectional observational study including 482 consecutive HIV-infected patients (mean age 53.9 ± SD 6.9 years; 75% male) attending the multidisciplinary metabolic clinic at the University of Modena, Italy. Frailty was measured with the frailty phenotype and a 37-item FI., Results: The mean FI score was 0.28±0.1 and frailty phenotype categories were: 3.1% frail, 51.9% pre-frail, and 45% robust. The duration of antiretroviral therapy was significantly different across levels of frailty as measured by both frailty tools (P < 0.01), but the nadir CD4 count was only significant for the FI (P = 0.01); current CD4 count was not significantly different across frailty levels using either tool. Both frailty measures were associated with multimorbidity; the FI was associated with Instrumental Activities of Daily Living impairment and falls history, whereas the frailty phenotype was not., Conclusions: The frailty phenotype and the FI demonstrated similar characteristics in patients at a tertiary-level HIV clinic. The FI had a stronger association with age, nadir CD4 count, comorbidities, falls, and disability. Integrating frailty assessments in clinical practice will be crucial for the development of interventions in age-related conditions, including disability and falls, in older persons living with HIV., (© 2017 British HIV Association.)

Background: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV., Methods: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405-720; nadir CD4 count 180, 81-280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection)., Results: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05-1.07), female sex (RR 0.93, 95% CI 0.87-0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93-0.99), duration of HIV infection (RR 1.06, 95% CI 1.01-1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02-1.14), and smoking pack-years (1.03, 1.01-1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02-1.38), current CD4 count (0.34, 0.20-0.60), and IDU (2.89, 1.30-6.42)., Conclusions: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV.

Background: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015., Methods: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity)., Results: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01)., Conclusions: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

Background: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients., Methods: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity., Results: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs., Conclusions: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.

Aging with HIV poses unique and complex challenges, including avoidance of neurocognitive disorder. Our objective here is to identify the prevalence and predictors of successful cognitive aging (SCA) in a sample of older adults with HIV. One hundred three HIV-infected individuals aged 50 and older were recruited from the Modena HIV Metabolic Clinic in Italy. Participants were treated with combination antiretroviral therapy for at least 1 year and had suppressed plasma HIV viral load. SCA was defined as the absence of neurocognitive impairment (as defined by deficits in tasks of episodic learning, information processing speed, executive function, and motor skills) depression, and functional impairment (instrumental activities of daily living). In cross-sectional analyses, odds of SCA were assessed in relation to HIV-related clinical data, HIV-Associated Non-AIDS (HANA) conditions, multimorbidity (≥2HANA conditions), and frailty. A frailty index was calculated as the number of deficits present out of 37 health variables. SCA was identified in 38.8% of participants. Despite no differences in average chronologic age between groups, SCA participants had significantly fewer HANA conditions, a lower frailty index, and were less likely to have hypertension. In addition, hypertension (odds ratio [OR] = 0.40, p = .04), multimorbidity (OR = 0.35, p = .05), and frailty (OR = 0.64, p = .04) were significantly associated with odds of SCA. Frailty is associated with the likelihood of SCA in people living with HIV. This defines an opportunity to apply knowledge from geriatric population research to people aging with HIV to better appreciate the complexity of their health status.

Objectives: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity., Design and Methods: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004-2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors., Results: Two thousand, seven hundred and twenty participants (mean age 46 ± 8; 32% women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95% confidence interval 1.05-2.52), current CD4 cell count (0.48, 0.32-0.72), and injection drug use (2.51, 1.16-5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65-2.36), age (1.07, 1.05-1.09), female sex (0.61, 0.40-0.91), and current CD4 cell count (0.71, 0.59-0.85)., Conclusion: Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV-related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV.

Objective: People aging with HIV might have different health conditions compared with people who seroconverted at older ages. The study objective was to assess the prevalence of, and risk factors for, individual co-morbidities and multimorbidity (MM) between HIV-positive patients with a longer duration of HIV infection, and patients who seroconverted at an older age. We compared estimates across both groups to a matched community-based cohort sampled from the general population., Methods: We performed a case-control study including antiretroviral therapy (ART)-experienced patients who were HIV seropositive for ≥ 20.6 years ("HIV-Aging"), or who were seropositive for < 11.3 years ("HIV-Aged") having access in 2013 at the Modena HIV Metabolic Clinic. Patients were matched in a 1:3 ratio with controls from the CINECA ARNO database. MM was defined as the concurrent presence of >2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and MM., Results: We analysed 404 HIV-Aging and 404 HIV-Aged participants in comparison to 2424 controls. The mean age was 46.7 ± 6.2 years, 28.9% were women. Prevalence of HIV co-morbidities and MM were significantly higher in the HIV-positive groups compared to the general population (p<0.001) and a trend towards higher rates of MM was found in aging vs aged group. This difference turned to be significant in patients above the age of 45 years old (p<0.001)., Conclusions: People aging with HIV display heterogeneous health conditions. Host factors and duration of HIV infection are associated with increased risk of MM compared to the general population.

The increasing life spans of people infected with human immunodeficiency virus (HIV) reflect enormous treatment successes and present new challenges related to aging. Even with suppression of viral loads and immune reconstitution, HIV-positive individuals exhibit excess vulnerability to multiple health problems that are not AIDS-defining. With the accumulation of multiple health problems, it is likely that many people aging with treated HIV infection may be identified as frail. Studies of frailty in people with HIV are currently limited but suggest that frailty might be feasible and useful as an integrative marker of multisystem vulnerability, for organizing care and for comprehensively measuring the impact of illness and treatment on overall health status. This review explains how frailty has been conceptualized and measured in the general population, critically reviews emerging data on frailty in people with HIV infection, and explores how the concept of frailty might inform HIV research and care., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Effective therapies have transformed HIV infection into a chronic disease, and new problems are arising related to aging. This article reviews the aging process, age-related deficit accumulation and frailty, and how these might be affected by chronic HIV infection., Recent Findings: Aging is characterized by acceleration in the rate of unrepaired physiologic damage an organism accumulates. HIV infection is associated with many factors that might affect the aging process, including extrinsic behavioral risk factors and co-infections, and multiple intrinsic factors, including intercellular communication, inflammation, and coagulation pathways. Whether each factor affects the aging process, they likely result in an increase in the risk of adverse health outcomes, and so give rise to frailty, likely with several clinical manifestations., Summary: Age-related deficit accumulation is influenced by both the background or environmental rate of insults an organism sustains and the efficacy of intrinsic damage control and repair mechanisms. Both processes are likely affected in people living with HIV infection.