Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects

Impact of antiretroviral dosing and daily pill burden on viral rebound rates in naive patients receiving a tenofovir-based regimen

Methods A total of 480 ART-naive patients were selected from the GNOMO cohort. Incidence rate of viral rebound (VR = first of two consecutive VL>50 cp/ml) was calculated as number of events over PYFU and expressed at univariate and multivariate analysis as incidence rate ratio (IRR). Number of both pills and doses per day were used to define three different types of regimens: twice-a-day regimens (BID regimens); once-a-day regimens with 3 pills (high-pill QD [hp-QD]). Adjusted rates of viral rebound were estimated by Poisson regression using date of first HIV-RNA <50 c/ml as baseline. Follow-up was censored at the date of VR, death, or loss to follow-up

Evidence-based renewal of the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons

The Italian Society for Infectious and Tropical Diseases (SIMIT) in collaboration with the Technical Health Committee (Sections L and M) of the Italian Ministry of Health have supported the renewal of the recommendations for the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. This publication summarizes the latest updates to the 2017 version of the Italian Guidelines for the management of HIV-1 infected patients and the use of antiretroviral drugs. New recommendations were released framing the clinical questions the use of antiretrovirals according to the Patient Intervention Comparator Outcome (PICO) methodology and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Diagnostic tools for immunological and virological monitoring, when to start, what to start, optimization and therapeutic failure were updated in order to include the recommendation obtained with these newly developed methods. For a complete review of clinical and therapeutic relevant topics we refer the reader to the extended version of the Guidelines

Management of hepatitis C virus infection in patients with chronic kidney disease: position statement of the joint committee of Italian association for the study of the liver (AISF), Italian society of internal medicine (SIMI), Italian society of infectious and tropical disease (SIMIT) and Italian society of nephrology (SIN)

Hepatitis C virus (HCV) infection is now considered a systemic disease due to the occurrence of extra-hepatic manifestations. Among these, the renal involvement is frequent. HCV infection, in fact, is strongly associated with proteinuria and chronic kidney disease (CKD) and negatively affects the prognosis of renal patients. In the last few years, availability of more specific and effective drugs against HCV has dramatically changed the clinical course of this disease. These drugs may provide further advantages in the CKD population as a whole by reducing progression of renal disease, mortality rate and by increasing the survival of graft in renal transplant recipients. The strict pathogenetic and prognostic link between HCV infection and CKD requires an ongoing relationship among the healthcare professionals involved in the treatment of both HCV infection and CKD. Therefore, Scientific Societies involved in the care of this high-risk population in Italy have organized a joint expert panel. The aim of the panel is to produce a position statement that can be used in daily clinical practice for the management of HCV infected patients across the whole spectrum of renal disease, from the conservative phase to renal replacement treatments (dialysis and transplantation). Sharing specific evidence-based expertise of different professional healthcare is the first step to obtain a common ground of knowledge on which to instate a model for multidisciplinary management of this high-risk population. Statements cover seven areas including epidemiology of CKD, HCV-induced glomerular damage, HCV-related renal risk, staging of liver disease in patients with CKD, prevention of transmission of HCV in hemodialysis units, treatment of HCV infection and management of HCV in kidney transplantation

From current status to optimization of HCV treatment: Recommendations from an expert panel

Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

Impact of antiretroviral dosing and daily pill burden on viral rebound rates in naive patients receiving a tenofovir-based regimen

Methods A total of 480 ART-naive patients were selected from the GNOMO cohort. Incidence rate of viral rebound (VR = first of two consecutive VL>50 cp/ml) was calculated as number of events over PYFU and expressed at univariate and multivariate analysis as incidence rate ratio (IRR). Number of both pills and doses per day were used to define three different types of regimens: twice-a-day regimens (BID regimens); once-a-day regimens with 3 pills (high-pill QD [hp-QD]). Adjusted rates of viral rebound were estimated by Poisson regression using date of first HIV-RNA <50 c/ml as baseline. Follow-up was censored at the date of VR, death, or loss to follow-up

Managing the long surviving HIV patient : a proposal for a multidimensional first-level diagnostic assessment

We propose a multidimensional first-level diagnostic assessment easy to use in routine clinical practice to allow infectious disease specialists to have a general and complete overview of persons living with HIV. Following the Delphi method, articles published from January 1, 2011 on controlled trials, clinical reports and observational studies dealing specifically with HIV and its co-morbidities were selected for review by the authors. Participants in the poll were selected among clinicians and infectious diseases specialists, working in 38 different dedicated HIV centres in Italy. The participants were given access to a website dedicated to the project and received a standardized information package containing a synopsis of the study and a description of the Delphi process and the selected literature. A total of 131 Items were divided into 10 first-level survey areas: anamnesis, objective examination, infectious diseases, osteoporosis diagnosis, metabolic pathologies diagnosis, cardiovascular diagnosis, nephrologic diagnosis, hepatological diagnosis, central nervous system diagnosis, evaluation of quality of life (QoL). This simple and concise first level tool identifies a few areas of multi-organ diagnostic assessment beyond the infectivity area. The identification of these areas will allow us to find shared and validated evaluation procedures with the intent to increase the likelihood of early recognition of patients at risk of comorbidity development, in order to facilitate more effective prevention, thereby reducing the overall impact on the quality of life of patients affected by this chronic illness

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 &lt; 1.45, 26.4% 1.45-3.25 and 7.7% &gt; 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to &lt; 1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 &gt; 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4&gt; 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART