Lipid Metabolism and Cardiovascular Risk in HIV-1 Infection and HAART: Present and Future Problems

Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN

Cost of human immunodeficiency virus infection in Italy, 2007-2009: effective and expensive are the new drugs worthwhile?

Background: In recent years, the increased efficacy and effectiveness of antiretroviral treatment has led to longer survival of patients infected with human immunodeficiency virus (HIV), but has also raised the question of what happens to consumption of resources. Early highly active antiretroviral treatment (HAART), management of hepatitis C virus (HCV) coinfection, and expensive newly marketed drugs may affect the economic sustainability of treatment from the point of view of the National Healthcare Services. The present study aimed to provide information on the economic burden of HIV-positive patients resident in the Lombardy region using a three-year time horizon. Methods: This was a retrospective, observational, budget impact study, based on information collected for the period 2007–2009, including hospitalizations, outpatient services, and HAART and non-HAART drug utilization. Patients with confirmed HIV infection, aged >=18 years, resident in the Lombardy region, and followed at the "L Sacco" Hospital in Milan from 2007 to 2009 were eligible. Results: A total of 483 patients (mean age 44.1 years) were included in the study. The mean CD4+ cell count increased over the study period from 462 ± 242 cells/mm3 in 2007, to 513 ± 267 cells/mm3 in 2008, to 547 ± 262 cells/mm3 in 2009. In total, 162 subjects (33.5%) were coinfected with HCV. Hospitalizations and HAART costs increased from 2007 to 2009, whereas outpatient visits and non-HAART drug costs decreased slightly over time. The total cost increase was also significant when limiting the analysis to experienced patients, HCV-negative patients, and experienced HCV-negative patients. Conclusion: CD4+ cell count, a major predictor of costs, increased over the study period. However, immunological improvement was achieved by greater expense in the short term. Whether this may be compensated by a long-term decrease in opportunistic infections and in the costs of management of HIV-related events is an area still to be investigated

Applicazione dell'approccio patient based per la determinazione dei costi sanitari diretti pubblici della cura e assistenza per l'infezione da HIV

La possibilità di stimare in modo accurato l'assorbimento di risorse economiche del Servizio Sanitario Regionale (SSR) in base alle caratteristiche della popolazione residente, risulta essere di centrale rilevanza per poter programmare accuratamente la spesa legata ai servizi erogati all'utenza. Attraverso l’esempio di una ricerca condotta su una coorte di pazienti HIV positivi afferenti all’Azienda Ospedaliera "Ospedale Luigi Sacco" di Milano, viene mostrato come l’utilizzo di un approccio patient based nella determinazione dei costi sanitari diretti pubblici, attraverso l'integrazione di database di tipo clinico e amministrativo (spese per terapia antiretrovirale, altri farmaci, specialistica ambulatoriale e ospedalizzazioni negli anni 2004-2007) dà la possibilità di individuare quali caratteristiche cliniche possono portare ad un aumento dei costi per il SSR e poter stimare costi standard per patologia, offrendo uno strumento per il monitoraggio dell'andamento della spesa e per il controllo dell'appropriatezza delle cure.The forecasting of economic resources utilisation of the resident population for a Regional Healthcare Service, based on its clinical characteristics, it is of high relevance in order to plan the regional healthcare budget. The usefulness of a patient based approach to determine public direct healthcare costs is presented through research conducted within Regione Lombardia on a cohort of HIV positive patients referring to Hospital Authority “Ospedale Luigi Sacco”, Milan. All the costs related to HAART , other drugs, outpatient and inpatient activity between 2004 and 2007 were assessed, integrating information within clinical and administrative databases. This allowed the possibility to identify the clinical characteristics which lead to an increase of costs for a Regional Healthcare System, and to assess standard costs per pathology, providing a tool to monitor the costs trends and to control the appropriateness of healthcare services

Raltegravir central nervous system tolerability in clinical practice: results from a multicenter observational study

Central nervous system (CNS) symptoms have been reported in clinical trials and case reports in patients receiving raltegravir. We investigated CNS symptoms in 453 HIV-infected patients. Of these 47 (10.4%) developed at least one drug-related CNS symptom. Predictors of CNS symptoms were concomitant therapy with tenofovir or with proton pump inhibitors that can increase raltegravir concentration. Thus, our data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms, and therefore their monitoring in clinical practice

Health care expenditure for HIV-patients by Health States

20-22 June 201

The cost of HIV disease in Northern Italy: the payer's perspective

Background: Healthcare expenditures incurred by the Health Service for HIV-infected patients have not been reported in Italy. Objective: To present health care costs for HIV-infected patients in the Lombardy Region, in 2004-2007, to determine the clinical characteristics of HIV infection associated with costs. Methods: Retrospective, observational, budget impact study, based on information collected for the period 2004-2007, including hospitalizations, outpatient services, highly active antiretroviral therapy (HAART) and non-HAART drug utilization. Inclusion criteria includes: confirmed HIV infection, age ≥18 years, resident in Lombardy Region, and followed at the “L. Sacco” Hospital in Milan from 2004 to 2007. Results: The mean total cost per year to provide healthcare to HIV-positive patients was rather stable (€9658.36 in 2004 and €9745.65 in 2007 (+0.90%)); HAART represented more than 60% of the total cost. We found that hepatitis C virus coinfection was related to higher costs (€11,003.45 vs. €8896.06), as well as CD4 cell count <200 cells/mm3 (€12,681.36 vs. €9594.11 and €9450.36 in 200-499 and ≥500 cells/mm3, respectively). The mean total cost of HIV health care was higher in patients who initiated antiretroviral treatment before 1997 than in those who started after 1996. Conclusions: The mean total cost per year to provide health care to HIV-positive patients was stable during the period 2004-2007, with an increase of HAART percentage impact on the total cost. Several clinical characteristics of HIV-infected patients were significantly associated with cost variation

Gender differences in HIV infection: is there a problem? analysis from the SCOLTA cohorts

Objectives: Evaluate gender differences with regard to baseline characteristics and outcome of therapy in cohorts of the SCOLTA (surveillance cohort long-term toxicity of antiretrovirals) project. Methods: The SCOLTA project is an active pharmacovigilance system for new antiretroviral drugs. Since 2002, patients were enrolled in nine cohorts (lopinavir, tenofovir, atazanavir, fosamprenavir, enfuvirtide, tipranavir, darunavir, raltegravir and maraviroc). Results: Two thousand one hundred and fifty-four patients were included in 5 PI cohorts; 607 (28.2%) were female. Women were younger and less frequently HCV-coinfected than men. At study entry, they were less frequently in CDC stage C, but CD4+ cells/mm3 and detectable HIV-RNA were not different by gender. Women had triglycerides alterations less frequently than men, but showed a higher proportion of low HDL-cholesterol. Women were protected from incident grade 2-4 triglycerides increase (odds ratio = 0.39, 95% confidence interval 0.18–0.88; P = 0.02). Mean CD4+ cell count increased in both men and women; despite a non-significantly lower initial CD4+ level, women had a better immunological recovery. Women discontinued PI treatment for adverse events and their own will more frequently. Conclusions: In these cohorts, gender distribution mirrored the Italian HIV population. Women were younger than men when they started their first ARV therapy and when they entered our cohorts. On the same treatment, they had a better immune response, though no significant difference emerged on virologic control and treatment durability. As compared to men, women appeared at lower risk of hypertriglyceridaemia. They stopped PI-based treatment of their own will more frequently than men, suggesting the need for a focused effort on adherence.</br

Statins and Aspirin use in HIV-infected people: gap between European AIDS Clinical Society guidelines and clinical practice: the results from HIV-HY study

To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice