Marianna Menozzi

Premature Age-Related Comorbidities Among HIV-Infected Persons Compared With the General Population

BACKGROUND Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. METHODS We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. RESULTS There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/μL (OR, 4.46), and ART exposure (OR, 1.01). CONCLUSIONS Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.

A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity

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.

Aging with HIV vs. HIV seroconversion at older age: a diverse population with distinct comorbidity profiles.

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.

Cost of noninfectious comorbidities in patients with HIV

Objectives We hypothesized that the increased prevalence of noninfectious comorbidities (NICMs) observed among HIV-infected patients may result in increased direct costs of medical care compared to the general population. Our objective was to provide estimates of and describe factors contributing to direct costs for medical care among HIV-infected patients, focusing on NICM care expenditure. Methods A case-control study analyzing direct medical care costs in 2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were compared to age, sex, and race-matched adults from the general population, included in the CINECA ARNO database (controls). NICMs evaluated included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Medical care cost information evaluated included pharmacy, outpatient, and inpatient hospital expenditures. Linear regression models were constructed to evaluate predictors of total care cost for the controls and cases. Results There were 2854 cases and 8562 controls. Mean age was 46 years and 37% were women. We analyzed data from 29,275 drug prescription records. Positive predictors of health care cost in the overall population: HIV infection (β = 2878; confidence interval (CI) = 2001–3755); polypathology (β = 8911; CI = 8356–9466); age (β = 62; CI = 45–79); and ART exposure (β = 18,773; CI = 17,873–19,672). Predictors of health care cost among cases: Center for Disease Control group C (β = 1548; CI = 330–2766); polypathology (β = 11,081; CI = 9447–12,716); age < 50 years (β = 1903; CI = 542–3264); protease inhibitor exposure (per month of use; β = 69; CI = 53–85); CD4 count < 200 cells/mm3 (β = 5438; CI = 3082–7795); and ART drug change (per change; β = 911; CI = 716–1106). Conclusion Total cost of medical care is higher in cases than controls. Lower medical costs associated with higher CD4 strata are offset by increases in the care costs needed for advancing age, particularly for NICMs.

Hypertriglyceridemia and Waist Circumference Predict Cardiovascular Risk among HIV Patients: A Cross-Sectional Study

Background Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. Methods 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. Results The high TG/high WC men had the most VAT (208.0±94.4 cm2), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3±6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0±97.9 cm2) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9±2.8) by comparison to low TG/low WC women (p<0.05 for all). Conclusions A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients.

Life expectancy in the immune recovery era: the evolving scenario of the HIV epidemic in northern Italy.

Introduction:National cohort and intercohort studies have been set to describe the differences of life expectancy (LE) of HIV-infected individuals. Objective:The aim of this study was to assess the impact of immune recovery (IR) on LE of patients with HIV undergoing combination antiretroviral therapy. Methods:In this retrospective observational study, outcome measure was LE of patients with HIV compared with LE of northern Italian population. Group categorizations were as follows: patients with no immune recovery (nIR), patients with IR, patients who are immune maintained, and pre-highly active antiretroviral therapy (HAART) and post-HAART. Abridged life tables were constructed from age-specific mortality rates (per 1000 person years) to estimate LE from the age of 20–55 years. Results:A total of 9671 patients, 71% men, were included. After 2005, we assisted to a rapid increase in the overall rate of patients attaining IR in the community coupled with a progressive decrease of AIDS death, but not of non-AIDS deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) = 2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group and nIR, respectively, compared with 41.38 years of the general Italian population. An approximately 5-year gap in LE was observed in IR patients. Discussion:We describe IR at a “community” level, related to calendar year and apparent 10 years after HAART introduction. HAART community IR is significantly influencing LE and is associated with the changing clinical picture of HIV disease. An increasing gradient of LE exists between nIR, post-HAART, and IR groups, with the latter, above the age of 40 years only, reaching LE of general population.

Human immunodeficiency virus infection is associated with accelerated atherosclerosis

OBJECTIVES Cardiovascular risk is increased in HIV-infected individuals compared with the general population, making HIV disease an ideal model to investigate the pathogenesis and natural history of atherosclerosis. In this pilot study, we compared the progression of coronary artery calcium (CAC) between HIV-infected and uninfected patients. METHODS Atherosclerosis progression was assessed in 25 HIV-infected men and 13 HIV-negative controls by means of sequential CAC scans using CT. A CAC score progression ≥ 15%/year was used as a surrogate marker of increased risk of cardiovascular events. RESULTS During a median follow-up of 11 months, a CAC score increase ≥ 15%/year was detected in 14 HIV-infected patients (56%) and 4 HIV-negative individuals (31%). HIV infection, age and hypercholesterolaemia were independently associated with a CAC score increase ≥ 15%/year in an adjusted Cox regression model. CONCLUSIONS HIV infection, age and hypercholesterolaemia were independently associated with CAC progression. HIV as well as traditional risk factors contribute to accelerate atherosclerosis in HIV-infected patients.

Epicardial adipose tissue and coronary artery calcium predict incident myocardial infarction and death in HIV-infected patients

BACKGROUND Epicardial adipose tissue (EAT) and coronary artery calcium (CAC) have been associated with incident coronary artery disease (CAD) and all-cause mortality in the general population. Their prognostic impact in HIV is unknown. METHODS Observational study of 843 consecutive HIV-infected patients receiving antiretroviral therapy for at least 6 months. Risk stratification was performed with coronary artery calcium (CAC) scoring and EAT screening. Patients were followed for CAD and all-cause mortality for a median of 2.8 years accounting for a total of 2572 patient-year follow-up. RESULTS Mean patient age was 50 ± 8 years and 69% were men. At baseline EAT was associated with male gender, age, waist circumference, visceral adipose tissue, and lipodystrophy, while CAC score ≥ 100 was associated with male gender, age and total cholesterol. During follow-up 33 patients suffered an event (15 incident myocardial infarctions and 18 deaths); the EAT volume was larger and the CAC score was higher in patients with events (p = 0.038 and p = 0.001 respectively). Multivariable regression analyses demonstrated that the upper tertile of EAT (≥ 93 cc; OR 2.15, 95% CI 1.06 - 4.39, p = 0.034), and CAC score ≥ 100 (OR 3.37, 95% CI 1.49 - 7.60, p = 0.003) were independent predictors of events after adjusting for age and sex. CONCLUSIONS In this observational cohort of HIV patients, EAT and CAC were independent predictors of hard outcomes after a median follow-up of approximately 3 years.

CD4/CD8 ratio is not predictive of multi-morbidity prevalence in HIV-infected patients but identify patients with higher CVD risk

CD4/CD8<0.8 is a surrogate marker of immune‐activation/immunosenescence and independently predicts mortality in the HIV‐infected patients due to non‐AIDS related events. Most studies showed that patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. Primary objective of the study was to explore the impact of CD4/CD8<0.8 as independent predictor of HIV‐associated non‐AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with no previous history of cardiovascular disease (CVD) a particular insight is provided in the association between impact of CD4/CD8<0.8 and risk prediction of CVD or radiological markers of subclinical CVD.

Impact of polypharmacy on antiretroviral prescription in people living with HIV.

Objectives To evaluate the relationship between polypharmacy and ART, delivered as conventional multi-tablet three-drug regimens, single-tablet regimens or less-drug regimens (simplified mono or dual regimens). Methods We conducted a cross-sectional analysis of electronic data from the prospective Modena HIV Metabolic Clinic Cohort Study. We included the last clinical observation for each patient from January 2006 to December 2015. Polypharmacy was defined as the use of five or more medications (excluding ART). Multi-morbidity was classified as the presence of two or more non-infectious comorbidities. Factors associated with different ART regimens were analysed using multivariable multinomial logistic regression analyses with multi-tablet three-drug regimens as the reference. Results A total of 2944 patients (33.7% females) were included in the analysis. Multinomial logistic regression analysis identified polypharmacy to be negatively associated with single-tablet regimens [relative risk reduction (RRR) = 0.48, 95% CI = 0.28–0.81] independently from frailty (RRR = 0.68, 95% CI = 0.59–0.78), after correction for age, gender, HIV infection duration, current and nadir CD4 and calendar year. This association was not found comparing multi-tablet three-drug regimens and less-drug regimens. Conclusions Single-tablet regimens are less likely to be prescribed in patients with polypharmacy. Single-tablet regimens are perceived to be less flexible in patients with multi-morbidity and at higher risk of drug–drug interaction.