Search

Introduction: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics., Methods: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics., Results: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively., Conclusions: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches., (© 2024. The Author(s).)

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility., Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model., Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care., Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: Hepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C., Methods: We analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing., Results: Our phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV., Conclusion: This discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Stefano, Ismail, Leitner, Faleo, Alwazzeh, Mbisa, Fiore and Santantonio.)

Background: The current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia., Methods: From May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients., Results: A total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment., Conclusions: The results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fasano, Milella, Carbonara, Tundo, Minniti, Buccoliero, Maci, Lo Caputo and Santantonio.)

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression.

The novel SARS-CoV-2 coronavirus causes a severe respiratory syndrome referred to as coronavirus disease (COVID-19). The angiotensin-converting enzyme 2 (ACE-2) plays an important role as a cellular receptor for SARS-CoV-2 and is largely expressed in lungs, kidneys, heart and the gastrointestinal tract along with being shed in plasma. The ACE-2 gene and protein show a high level of genetic polymorphism, including simple nucleotide variation, transcriptional variation, post-transcriptional changes, and putative protein mutations that could interfere with the binding or entry of SARS-CoV-2 and affect tissue damage in lungs or other organs. Genetic polymorphisms can impact SARS-CoV-2 viral entry and COVID-19 severity. This single-center study evaluated the possible role of the main ACE-2 polymorphisms (rs143936283, rs2285666, rs41303171, rs35803318, and rs2106809) as potential prognostic markers in SARS-CoV-2-infected individuals. Frozen whole blood was used for DNA isolation and genomic DNA samples were sheared using the Covaris LE220 Focused-ultrasonicator for targeting a peak size of 410 bp. Whole-genome sequencing libraries were generated from fragmented DNA using the Illumina TruSeq DNA PCR-Free HT Library Preparation Kit and sequenced on an Illumina NovaSeq 6000. We did not identify any correlation between ACE-2 polymorphisms and COVID-19 prognosis, suggesting that the interpretation and clinical use of ACE-2 genetic polymorphisms in real-world clinical settings requires further experimental and clinical validation.

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy., Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used., Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time., Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The study aimed to characterize the genotype and subgenotypes of HBV circulating in Saudi Arabia, the presence of clinically relevant mutations possibly associated with resistance to antivirals or immune escape phenomena, and the possible impact of mutations in the structural characteristics of HBV polymerase. Plasma samples from 12 Saudi Arabian HBV-infected patients were analyzed using an in-house PCR method and direct sequencing. Saudi patients were infected with mainly subgenotype D1. A number of mutations in the RT gene (correlated to antiviral resistance) and within and outside the major hydrophilic region of the S gene (claimed to influence immunogenicity and be related to immune escape) were observed in almost all patients. Furthermore, the presence of mutations in the S region caused a change in the tertiary structure of the protein compared with the consensus region. Clinical manifestations of HBV infection may change dramatically as a result of viral and host factors: the study of mutations and protein-associated cofactors might define possible aspects relevant for the natural and therapeutic history of HBV infection.

Introduction: Tuberculosis (TB) remains an unresolved global health problem and vulnerable groups such as migrants remain the most affected with a higher risk of worse outcomes. The aim of this study was to evaluate clinical features, outcomes, and adverse events in migrant and native Italian patients admitted to three Italian hospitals in Southern Italy in order to assess differences and targeted strategies., Methods: We performed a retrospective study on TB patients admitted between January 1, 2013, and December 31, 2021, in three Apulia hospitals. Two logistic regression models were used, with the dependent variables being (I) unsuccessful treatment (died, loss to follow-up, and failed treatment) and (II) adverse events., Results: We enrolled 543 consecutive patients admitted at three Italian hospitals with a diagnosis of TB during the study period, of them 323 (59.5%) were migrants and 220 Italian patients. The treatment success rate in the migrant group was 44.9% (137/305), while in the non-migrant group was 97.1% (203/209). Independent factors of unsuccess treatment (death, failure or loss to follow up) were: migrant status (O.R. = 11.31; 95% CI 9.72-14.23), being male (O.R. = 4.63; 95% CI 2.16-6.10), homelessness (O.R. = 3.23; 95% CI 2.58-4.54), having a MDR (Multidrug-resistant) (O.R = 6.44; 95% CI 4.74-8.23), diagnostic delay (O.R. = 3.55; 95% CI 1.98-5.67), and length of hospitalization (O.R. = 3.43; 95% CI 1.88-5.87). While, age >65 ys (O.R. = 3.11; 95% CI 1.42-4.76), presence of extrapulmonary TB (O.R. = 1.51; 95% CI 1.31-2.18), monoresistance (O.R. = 1.45; 95% CI 1.25-3.14) and MDR pattern (O.R. = 2.44; 95% CI 1.74-5.03) resulted associated with adverse events., Conclusion: Migrant population is at high risk of unsuccessful treatment (death, loss to follow-up, and treatment failure). Policies targeted specifically to this group are needed to really impact and improve their health status and also to contain the TB burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Gennaro, Cotugno, Fasano, Ricciardi, Ronga, Lattanzio, Grimaldi, Bavaro, Ciarallo, Garzone, De Iaco, Guido, Fiore, Brindicci, Santoro, Sica, Iacovazzi, Santantonio and Saracino.)

Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) has a more rapid progression than in HBV-monoinfected patients, leading to end-stage liver disease complications, including hepatocellular carcinoma. Therefore, the adequate management of CHB is considered a priority in HIV-coinfected patients. Several guidelines have highlighted this issue and have provided recommendations for preventing and treating HBV infection. This article discusses the management of liver disease in patients with HIV/HBV coinfection and summarizes the current and future therapeutic options for treating chronic hepatitis B in this setting.

Background: Italy experienced SARS-CoV-2 spread during the second wave and the southern regions were severely affected. In this prospective study, we assessed the changes in SARS-CoV-2 seroprevalence rates in non-vaccinated blood donors to evaluate the spread of SARS-CoV-2 among healthy individuals in our geographical area., Methods: 8,183 healthy blood donors visiting the Transfusion Centre at the University Hospital "Riuniti" of Foggia (Italy) to donate blood from May 2020 to March 2021 were tested twice for anti-SARS-CoV-2 antibodies by Ortho Clinical Diagnostics VITROS ® 3600 through anti-SARS-CoV-2 Total and IgG reagent kit. None of the subjects had diagnosed symptomatic COVID-19 infection, and none had received vaccination., Results: Overall, 516 out of 8,183 had antibodies to SARS-CoV-2 (total and IgG antibodies) (6.3%, 95% CI: 0.03-0.15%), 387 were male and 129 female. There was a significant increase of seropositive donors from May 2020 to March 2021 ( p  < .001). The difference in seroprevalence was significantly associated with age but not sex (2-sided p  < .05 for age; 2-sided p  ≥ .05 for sex) in both groups., Conclusions: Our study showed a significant increase in SARS-CoV-2 seroprevalence in blood donors and suggests that asymptomatic individuals might contribute to the spread of SARS-CoV-2. These results may contribute to revised containment measures, priorities in vaccine campaigns and monitoring of seroprevalence in public places like Transfusion Centres. Serologic testing of blood donors may be relevant to monitor SARS-CoV-2 circulation in the general population.

Background: SARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed., Material and Methods: We fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the "wild type" SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay., Results: NA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV., Discussion: The difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant., Conclusions: The administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garziano, Utyro, Poliseno, Santantonio, Saulle, Strizzi, Lo Caputo, Clerici, Introini and Biasin.)

The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment ( p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient's outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using χ2statistics. A p<0.05 was considered statistically significant. From December 2019 to February 2020, 672 patients completed the survey, 59% males and 56% >50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age >50years, lower education level, history of disease >10 years and residency in Northern Italy. The "Undetectable = Untrasmittable" (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p< 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable., Competing Interests: The authors have no conflict of interest to disclose.

Here we present results from a survey on anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in healthy blood donors from a low incidence coronavirus disease 2019 area (Apulia region, South Eastern Italy). Among 904 subjects tested, only in nine cases (0.99%) antibodies against SARS-CoV-2 were demonstrated. All the nine seropositive patients were negative for the research of viral RNA by reverse transcription polymerase chain reaction in nasopharyngeal swabs. These data, along with those recently reported from other countries, clearly show that we are very far from herd immunity and that the containment measures are at the moment the only realistic instrument we have to slow the spread of the pandemic., (© 2020 Wiley Periodicals LLC.)

Background: The highly variable manifestation of the COVID-19 disease, from completely asymptomatic to fatal, is both a clinical and a public health issue. The criteria for discharge of hospitalized patients have been based so far on the negative result of Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) tests, but the persistence of viral fragments may exceed that of the integral virus by weeks. The aim of our study was to verify the clearance of the virus at viral culture in patients hospitalized for COVID-19 that have clinically recovered but are still positive on nasopharyngeal swab., Methods: The study was conducted in hospitalized patients with positive RT-PCR on nasopharyngeal swab. Patients included were from asymptomatic to severe cases and performed nasopharyngeal control swabbing on day 14 for asymptomatic patient or at least three days after remission of symptoms. RT-PCR positive specimens were sent to a biosafety level 3 laboratory for viral culture., Results: We performed a combined analysis of RT-PCR and a highly sensitive in vitro culture from 84 samples of hospitalized patients. The average age was 46 ± 20.29, and 40.5% of the subjects had radiologically confirmed pneumonia, with average PaO 2 of 72.35 ± 12.12and P/F ratio of 315 ± 83.15. Ct values for the N gene were lower in the first swab than in the control one ( p < 0.001). The samples from 83 patients were negative at viral culture, and RT-PCR on the respective supernatants always confirmed the absence of viral growth., Conclusions: Our preliminary results demonstrate that patients clinically recovered for at least three days show the viral clearance at viral culture, and presumably they continued to not be contagious.

Recently, a significant cluster of pneumonia caused by a novel betacoronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) was described initially in China and then spread throughout the world. Like other coronaviridae, the viral transmission occurs mainly through droplets. In addition, the virus has been detected in different clinical specimens, suggesting a potential transmission by other routes, including blood transfusion. However, the potential risk of transmission of SARS-CoV-2 via blood products is still unclear. The aim of our study was to investigate the prevalence of antibodies against SARS-CoV-2 among blood donors from South-Eastern Italy. Moreover, in the seropositive donors, we searched for the presence of the virus in nasopharyngeal swabs and in plasma samples. Overall, 1,797 blood donors from the Apulia region were tested for anti-SARS-CoV-2 antibodies, using a commercially available assay. Only 18/1,797 donors (1.0%) tested positive for anti-SARS-CoV-2 antibodies; in none of them SARS-CoV-2 viral RNA was detected in nasopharyngeal swabs and in plasma samples. Our results indicate that most of the blood donors in Apulia remained uninfected during this wave of the pandemic; further, none had detectable virus both in nasopharyngeal swabs and in blood samples. The risk to carry and transmit the virus by healthy and asymptomatic blood donors is probably very low., (© 2021 S. Karger AG, Basel.)

Currently, treatment of chronic hepatitis C is based on a combination of direct-acting antiviral agents (DAAs) which achieve HCV clearance in more than 95% of patients. Despite this high rate of cure, treatment failures can occur in about 3-5% of treated patients. Resistance associated substitutions (RAS) are commonly detected after virological failure, although their role in real-life DAA failures is still debated. This study aimed to evaluate in real-life DAA-failing patients the prevalence of clinically relevant RASs for the different DAA classes and to identify possible predictors. Fifty consecutive HCV-infected patients who experienced a virological failure to a DAA-containing regimen were included in the study. Direct sequencing of HCV regions involved in DAA resistance (NS3, NS5A and NS5B) was performed with Sanger-based homemade protocols. The presence of mutations in the NS3 and NS5A regions was statistically associated with regimens containing protease inhibitors (p<0.0032) and NS5A inhibitors (p<0.0006), respectively. On the contrary, for the NS5B region, the known mutations associated with the NS5B RNA polymerase inhibitors were detected in treated HCV patients, although there was no statistical significance (p>0.5). A significant correlation was found between the presence of RASs and advanced fibrosis/cirrhosis, but not with age, sex and viral load. Our study demonstrates a high frequency of RASs in patients with DAA failure, thus highlighting the usefulness of genotypic tests in this setting. The identification of RASs may guide the choice of the most appropriate drugs for HCV re-treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of "Policlinico Riuniti", Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG-positive tests; 62 (1.9%; 95% CI: 1.4-2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5-2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5-2.5). Overall, within eight weeks, we detected a mean reduction of -17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R 2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia's hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections.

Objective: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated., Setting: Prospective, multicenter, single-country, noninterventional cohort study., Methods: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA <50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA <50 copies/mL, was measured at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography., Results: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P < 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046)., Conclusions: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides.

Background: Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated., Methods: Patients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis., Results: 93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6-44.6) and 24.6 (range 6.8-47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04-1.13), male sex (HR = 2.76; 95% CI 1.28-5.96), lower albumin levels (HR = 3.94; 95% CI 1.81-8.58), genotype 3 (HR = 5.05; 95% CI 1.75-14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01-3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00-1.07), male sex (HR = 2.13; 95% CI 1.06-4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89-7.46) were independently associated with the appearance of a decompensating event after viral eradication., Conclusion: Different demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.

Background: Suppression of hepatitis B virus (HBV) replication with nucelos(t)ide analogues should be considered for patients with chronic hepatitis D virus (HDV) infection and ongoing HBV replication., Aim: To verify the clinical outcome after long-term entecavir or tenofovir treatment in patients with advanced fibrosis/cirrhosis, ineligible to peg-interferon therapy., Methods: Patients were prospectively followed-up at 3-6 month intervals; measured outcomes were decompensation, hepatocellular carcinoma (HCC), liver transplant and liver related death. HBV monoinfected patients receiving the same treatment served as reference after 1:1 matching by age, gender, platelet count, albumin level, bilirubin and INR., Results: 56 HDV patients (48 with cirrhosis; median follow-up 50 months) were enrolled; all achieved HBV DNA suppression. Death or liver transplant occurred in 19 patients, with a rate (n/1000 patient-months) of 2.92 in HDV patients vs 0.38 in HBV monoinfected patients (P < 0.001); similarly, decompensation occurred at a rate of 1.53 vs 0.13 (P = 0.015), respectively, and the rate of HCC was almost thrice in HDV cohort (3.12 vs 1.12; P = 0.02) Platelet count, Child-Pugh score and marginally HDV infection were associated with HCC development., Conclusion: Patients with HDV infection and advanced liver disease maintain an increased risk of severe clinical events as compared with HBV monoinfected patients, during prolonged HBV DNA suppression with potent NA., (© 2019 John Wiley & Sons Ltd.)

Background & Aims: Advances in direct-acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked-to-care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030., Methods: Using a modelling approach grounded in Italian real-life data of diagnosed and treated patients, different linkage-to-care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals., Results: Under the 40% linked-to-care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948-1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0-F3 cases. Under the 60% linked-to-care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958-1978 birth cohorts could capture 55% of F0-F3 individuals. Under the 80% linked-to-care scenario, screening limited in 1968-1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals., Conclusion: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV) infection, with improved bone effects at 48 weeks. We performed a randomized trial to evaluate the bone safety of TAF compared with TDF over 2 years, assessing baseline risk factors for bone loss, were evaluated after 2 years of treatment., Methods: In a double-blind study, hepatitis B e antigen (HBeAg)-positive patients (n = 873) and HBeAg-negative patients (n = 425) were randomly assigned (2:1) to groups given TAF (25 mg; n = 866) or TDF (300 mg; n = 432) once daily. We assessed bone safety, including hip and spine BMD, using dual-energy X-ray absorptiometry and measured changes in serum markers of bone turnover over 96 weeks., Results: At baseline, treatment groups were well matched. At week 96, patients receiving TAF had significantly smaller decreases in hip BMD (mean reduction of 0.33%) than patients receiving TDF (mean reduction of 2.51%) (P < .001) and spine BMD (reduction of 0.75% in patients receiving patients receiving TAF vs reduction of 2.57% in patients receiving TDF) (P < .001). For hip BMD, the magnitude of difference in bone loss between the TAF and TDF groups increased at week 96 compared to week 48 (P < .001). The TAF group had minimal changes in markers of bone turnover by 12 weeks of treatment, but the TDF group had significant changes, compared to baseline. Risk factors for bone loss had fewer effects in patients receiving TAF than TDF at week 96., Conclusions: In double-blind randomized trials, we found that after 2 years of treatment, patients receiving TAF had continued improvements in bone safety compared with patients receiving TDF. Clinicaltrial.gov ID NCT01940471 and NCT01940341., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: HIV infection is a known prothrombotic condition but factors involved are still controversial. A role for antiretrovirals, especially protease inhibitors, was advocated., Objectives: The study aimed to analyze the levels of anticoagulant proteins in virally suppressed HIV-infected subjects treated with different anti-retroviral regimens., Materials and Methods: Forty-four patients were included in the study. C and PS, D-Dimers and Fibrinogen levels were determined as well as APC-resistance. PROS1 gene was sequenced in a group of patient., Results: Twelve of the 44 subjects (27%) showed reduced levels of PS, while lower levels of PC were found only in 2 patients (4,5%). No difference in the mean values of PC and PS was found stratifying the study population by antiretroviral regimen administrated (p>0.05).Three patients had higher levels of D-Dimer concentrations and in two of these patients, an association between higher D-Dimer values and lower levels of PS was observed; but however no correlation was found by statistical analysis.PROS1 gene analysis was performed in 26 of the 44 HIV-1 patients and the subjects with low levels of PS had mutation in the fifteen exon of PROS 1 gene. While among individuals with normal levels, this mutation was observed only in 8/18 (44%) of the cases (p=0,0072)., Conclusion: The majority of patients with low PS levels also had mutations in the fifteen exon of PROS 1 gene. Genetic determinants, deserving further investigations, rather than antiretrovirals might cause PS deficiency in HIV-1 positive patients.

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis., Conclusion: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814-1825)., (© 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Background: Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure., Aim: To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage., Methods: Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers., Results: Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications., Conclusions: Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

Background: Migrants in Italy are prevalently young adults, with a higher risk of sexual transmitted infections (STI) and HIV infection. Promoting consistent as well as correct use of condoms could reduce failure rate due to their improper use. The aim of our study was to evaluate Condom Use Skills among a migrant population recently landed in Italy, hosted in a government center for asylum seekers., Methods: The study sample was composed of 80 male migrants. Sanitary trained interviewers submitted a questionnaire to participants to investigate age, provenience, marital status, educational level and knowledge about transmission and prevention of HIV/STI. Then, we assessed participants' level of condom use skill with the Condom Use Skills (CUS) measure by using a wooden penile model. The interviewer filled in a checklist and assigned 1 point for correct demonstration of each behavior that may prevent condom failure during sex., Results: Participants' median age was 26 years and the sample was composed of 54 migrants from sub-Saharan Africa and 26 from Middle East. Most of them were married, with a lower middle level of education, up to 8 or 5 years. Half of the sample achieved the highest score in the questionnaire and our CUS showed a large number of people with middle high score classes. The Spearman's rho was 0.30, therefore answers to the questionnaire and CUS score appeared correlated (p < 0.05). In the multivariate model, to have a higher CUS score resulted to be associated to be older than 26 years (p < 0.05), with a higher level of education (p = 0.001), and a higher score in the questionnaire (p < 0.05). There were no significant differences in the level of CUS between single or married men and between African and Middle Asian migrants of the sample., Conclusions: Our study shows that educational level influences the quality of knowledge and awareness about STI/AIDS and contribute to correct condom use. Since the half of participants had a low educational level and linguistic problems, the risk of missing campaigns messages or misunderstanding informative materials increases. Direct observation of condom-application on penile model may offer realistic assessment of application skills in these individuals.

Background and Aim: Tenofovir disoproxil fumarate (TDF) is recommended as first-line monotherapy for nucleos(t)ide (NA)-naïve chronic hepatitis B (CHB) patients and as a second-line rescue therapy for NA-experienced patients with a previous treatment failure. However, data regarding the efficacy of TDF monotherapy in patients with lamivudine resistance (LAM-R) successfully treated with LAM+adefovir (ADV) are limited. Herein, the efficacy and safety of switching from LAM+ADV to TDF monotherapy in clinical practice have been evaluated., Methods: Sixty LAM-R HBeAg-negative CHB patients treated with ADV add-on therapy and stable viral suppression, were switched to TDF monotherapy and prospectively evaluated for virological response, liver and renal function, and bone mineral density., Results: During a median period of 57 months of TDF monotherapy, all patients maintained a virological response, four of whom cleared HBsAg (6.6%) and discontinued treatment. Monitoring of renal function showed no case of the Fanconi syndrome, no significant alterations of median serum creatinine, eGFR and phosphate levels, although a reduction of TDF dosage was required in five patients (8.3%). Despite the stable virological suppression, five cirrhotic patients and one CHB patient developed hepatocellular carcinoma., Conclusions: Our results demonstrate the efficacy of switching to TDF monotherapy in virologically suppressed CHB patients receiving long-term LAM+ADV therapy, with a low rate of adverse events., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: The incidence and consequences of flares during first-line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of alanine aminotransferase (ALT) flares during long-term entecavir (ETV) in chronic hepatitis B (CHB)., Methods: CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as > 3× increase in ALT compared with baseline or lowest on-treatment level and an absolute ALT > 3× ULN. Flares were designated as host-induced (preceded by hepatitis B virus (HBV)-DNA decline), virus-induced (HBV-DNA increase), or indeterminate (stable HBV-DNA)., Results: Seven hundred and twenty-nine patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline hepatitis B e antigen (HBeAg)-positivity (HR 2.84; P = 0.005) and high HBV-DNA (Hazard ratio (HR) 1.30; P = 0.003) predicted flares. There were 12 (40%) host-induced, 7 (23%) virus-induced, and 11 (37%) indeterminate flares. Host-induced flares occurred earlier than virus-induced (median: 15 vs 83 weeks; P = 0.027) or indeterminate flares (15 vs 109 weeks; P = 0.011). Host-induced flares were associated with biochemical remission, and HBeAg (n = 3) and hepatitis B surface antigen (n = 2) seroconversions were exclusively observed among patients with these flares. Virus-induced flares were associated with ETV resistance (n = 2) and non-compliance (n = 1)., Conclusion: The incidence of ALT flares during ETV was low in this real-life cohort. ETV can be safely continued in patients with host-induced flares. Treatment adherence and drug resistance must be assessed in patients with virus-induced flares., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The efficacy data obtained with boceprevir and telaprevir for persons with hepatitis C virus (HCV) genotype 1 infection raise the question of whether HCV protease inhibitors should be used in human immunodeficiency virus (HIV)/HCV co-infected persons. The Italian Association for the Study of Infectious and Tropical Diseases has made these recommendations to provide the rationale and practical indications for the use of triple anti-HCV therapy in persons living with HIV (PLWHIV). A Writing Committee of experts indicated by the President of the Association and a Consulting Committee con- tributed to the document. The final draft was submitted to the evaluation of external experts and the text modified according to their suggestions and comments. Treatment of HCV co-infection should be considered for all HCV RNA positive PLWHIV. Response-guided therapy with pegylated interferon and ribavirin is the standard treatment of PLWHIV with infection by HCV genotype 2, 3, 4, 5 and 6. Boceprevir and telaprevir should be used to treat HCV genotype 1 infection in HIV/HCV co-infected patients for 48 weeks on an individual basis, with close monitoring of their efficacy and tolerability with concur- rent antiretroviral therapy, taking into account potential drug-drug interactions. The decision to treat a patient or to wait for better treatment options, or to discontinue treatment should be made on an individual basis taking into account pre-treatment variables and the on-treatment HCV RNA kinetics.