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Objective: The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI., Design: A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy., Methods: PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR., Results: We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition., Conclusion: A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint that could be used in clinical and research settings., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim was to investigate the contribution of liver steatosis and significant fibrosis alone and in association [nonalcoholic fatty liver disease (NAFLD) with fibrosis] to frailty as a measure of biological age in people living with HIV (PLWH)., Design: This was a cross-sectional study of consecutive patients attending Modena HIV Metabolic Clinic in 2018-2019., Methods: Patients with hazardous alcohol intake and viral hepatitis coinfection were excluded. Liver steatosis was diagnosed by controlled attenuation parameter (CAP), while liver fibrosis was diagnosed by liver stiffness measurement (LSM). NAFLD was defined as presence of liver steatosis (CAP ≥248 dB/m), while significant liver fibrosis or cirrhosis (stage ≥F2) as LSM at least 7.1 kPa. Frailty was assessed using a 36-Item frailty index. Logistic regression was used to explore predictors of frailty using steatosis and fibrosis as covariates., Results: We analysed 707 PLWH (mean age 53.5 years, 76.2% men, median CD4 cell count 700 cells/μl, 98.7% with undetectable HIV RNA). NAFLD with fibrosis was present in 10.2%; 18.9 and 3.9% of patients were classified as frail and most-frail, respectively. Univariate analysis demonstrated that neurocognitive impairment [odds ratio (OR) = 5.1, 1.6-15], vitamin D insufficiency (OR = 1.94, 1.2-3.2), obesity (OR = 8.1, 4.4-14.6), diabetes (OR = 3.2, 1.9-5.6), metabolic syndrome (OR = 2.41, 1.47-3.95) and osteoporosis (OR = 0.37, 0.16-0.76) were significantly associated with NAFLD with fibrosis. Predictors of frailty index included steatosis (OR = 2.1, 1.3-3.5), fibrosis (OR = 2, 1-3.7), NAFLD with fibrosis (OR = 9.2, 5.2-16.8), diabetes (OR = 1.7, 1-2.7) and multimorbidity (OR = 2.5, 1.5-4)., Conclusion: Liver steatosis and NAFLD with fibrosis were associated with frailty. NAFLD with fibrosis exceeded multimorbidity in the prediction of frailty, suggesting the former as an indicator of metabolic age in PLWH.

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.

Background: Epicardial adipose tissue (EAT) is increased in HIV-infected patients. The aim of this study was to evaluate the association between EAT and coronary artery calcium (CAC) a marker of atherosclerosis; furthermore, we investigated the association of EAT with HIV infection, antiretroviral therapy (ART), and lipodystrophy., Methods: This was a cross-sectional study of 876 consecutive HIV-infected ART experienced patients. Patients underwent CAC imaging with multidetector computed tomography (CT) for atherosclerosis screening and risk of cardiovascular events (CAC score >100); EAT was measured in the same CT images. Factors independently associated with EAT were explored in a multivariable backward stepwise linear regression analysis. Multivariable logistic regression was used to evaluate the association of EAT and CAC score greater than 100., Results: Patients' mean age was 47.2 ± 8 years, 68% were men. EAT was associated with central fat accumulation and mixed lipodystrophy phenotypes. Factors independently associated with EAT were: age [β = 0.6, confidence interval (CI) 0.2-1.0], male sex (β = 6.6, CI 0.5-12.7), visceral adipose tissue (β = 0.12, CI 0.08-0.17), waist circumference (β = 0.7, CI 0.04-1.3), current CD4⁺ (β = 0.6, CI 0.1-1.2, per 50 cells), total cholesterol (β = 0.1, CI 0.02-0.15), and cumulative exposure to ART (months) (β = 0.05, CI 0.00-0.11). EAT (per 10 cm³) was associated with CAC greater than 100 (odds ratio = 1.10, CI 1.02-1.19) after adjustment for age, male sex, and diabetes., Conclusion: We showed an association between EAT and central fat accumulation and mixed form lipodystrophy phenotypes as well as traditional risk factors for atherosclerosis. EAT may be a useful marker of cardiovascular risk as shown by its association with CAC greater than 100.

Background: Metabolic complications, including type 2 diabetes mellitus and metabolic syndrome, are increasingly recognized among HIV-infected individuals. Low vitamin D levels increase the risk of type 2 diabetes mellitus, and vitamin D supplementation has been shown to decrease the risk of type 2 diabetes mellitus in patients without HIV infection., Objectives: The primary objective was to determine whether vitamin D deficiency (serum 25-hyrdoxyvitamin D <20 ng/ml) was associated with type 2 diabetes mellitus among HIV-infected patients. Our secondary objective was to determine whether vitamin D deficiency was associated with metabolic syndrome in HIV., Methods: We conducted a cross-sectional study among participants enrolled in the prospective Modena (Italy) HIV Metabolic Clinic Cohort. Clinical and laboratory data, including history of type 2 diabetes mellitus, fasting blood glucose, components of metabolic syndrome, and 25-hydroxyvitamin D levels, were obtained for all participants., Results: After adjusting for vitamin D supplementation, sex, age, body mass index, and hepatitis C virus co-infection, vitamin D deficiency was associated with type 2 diabetes mellitus [adjusted odds ratio (OR) 1.85; 95% confidence interval (CI) 1.03-3.32; P = 0.038]. The association between vitamin D deficiency and metabolic syndrome was not significant after adjusting for vitamin D supplementation, sex, age and body mass index (adjusted OR 1.32; 95% CI 1.00-1.75; P = 0.053)., Conclusions: Our study demonstrates an association between vitamin D deficiency and type 2 diabetes mellitus. Clinical trials are needed to better characterize the association between vitamin D deficiency and type 2 diabetes mellitus in HIV infection and to evaluate whether vitamin D is able to prevent or delay the onset of type 2 diabetes mellitus.