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Highlights • Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. • The effects of canakinumab in patients with COVID-19-related pneumonia were studied. • 33 patients received canakinumab and 15 received institutional standard of care. • Treatment with canakinumab rapidly restored normal oxygen status. • Canakinumab was also associated with favorable prognosis versus SoC., Objectives Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. We studied the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design The aim of our study was to evaluate the reduction in duration of hospitalization with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study; 33 patients (Cases) signed informed consent and received canakinumab (Cohort 1); 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (SoC), (Cohort 2). Results Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs 26 days, respectively; p

Background An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virological failure (VF) over time among migrants to Italy enrolled in ARCA. Methods HIV-1 sequences from ART-naive patients of non-Italian nationality were retrieved from ARCA database from 1998 to 2017. PDR was defined by at least one mutation from the reference 2009 WHO surveillance list. Results Protease/reverse transcriptase sequences from 1,155 patients, mainly migrants from sub-Saharan Africa (SSA; 42%), followed by Latin America (LA; 25%) and Western countries (WE; 21%), were included. PDR was detected in 8.6% of sequences (13.1% versus 5.8% for B and non-B strains, respectively; PConclusions PDR appeared to be stable over the years in migrants to Italy enrolled in ARCA; however, it still remains an important cause of VF together with viral load at diagnosis.

Background & Aims Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. Methods All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. Results A total of 179 patients were included: median age 57 (18–88) years, 74% males, median HCV-RNA 1,081,817 (482–25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). Conclusions SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. Lay summary This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.

Background Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6–97.2) without M184V and 87.8% (95% CI, 78.4–97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51–199 copies/mL) was 79.8% (95% CI, 67.8%–91.8%) with M184V vs 90.1% (95% CI, 84.0%–96.2%) without M184V (P = .016). Conclusions Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

Background The risk of liver enzyme elevation (LEE) after different ritonavir-boosted protease inhibitors (PI/r) has not been fully assessed in real-life settings and in populations with high rates of hepatitis C virus (HCV) coinfection. Methods Patients introducing a new PI/r between 1998 and 2012 were included, if transaminases and HCV antibody (Ab) were assessed before treatment initiation. Time to grade 3 and 4 LEE were assessed using univariable and multivariable conditional Cox analyses, stratified by HCV serostatus. Results A total of 6193 HIV-infected patients (3242 HCV-Ab negative and 2951 HCV-Ab positive) were included. Incidence of grade 3 LEE was 1.05, 7.66, and 8.08 per 100 patient-years of follow-up among HCV-Ab negative, HCV-Ab-positive and HCV-RNA-positive patients, respectively. Among HCV-Ab-negative patients, no differences were detected between different PI/r. Use of darunavir/ritonavir was not associated with LEE among HCV-coinfected patients. Atazanavir/ritonavir use was associated with grade 3 LEE but only among HCV-Ab-positive patients (versus LPV/r, hazard ratio: 1.39; 95% confidence interval: 1.1 to 1.75). This risk was not confirmed in a subanalysis restricted to HCV-RNA-positive patients (versus LPV/r, hazard ratio: 1.16; 95% confidence interval: 0.87 to 1.55). Other independent predictors of grade 3 LEE among HCV-Ab-positive patients were older age, male gender, being treatment naive, nonnucleoside reverse transcriptase inhibitor coadministration, increased aspartate aminotransferase at baseline, overweight, positive HCV-RNA, and advanced estimated liver fibrosis. Conclusions Occurrence of hepatotoxicity was a rare finding among HCV-Ab-negative patients and was not influenced by the type of PI/r. In particular, the use of darunavir/ritonavir, previously linked with severe cases of hepatotoxicity, was not associated with a greater risk of LEE, irrespective from HCV serostatus.

To the Editor: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has been identified in livestock animals (particularly pigs), veterinarians, and animal farm workers (1,2). CA-MRSA strains from pigs have been classified most frequently within the multilocus sequence type (ST) 398 (1) and have been rarely identified as a cause of invasive infection in humans (1,3,4). We report a case of invasive infection in a pig-farm worker in Cremona, Italy, an intensive animal farming area; the infection was caused by MRSA of swine origin, ST398. The case-patient was a 58-year-old man admitted to a surgical department in Cremona, Italy, on July 30, 2007, because of a 1-week history of fever and intense pain in his right buttock. He worked on a pig farm, was obese, consumed high volumes of wine (1.5 L/day), was taking medication for hypertension, and had not had recent (

About 40% of the Italian HIV-1 epidemic due to non-B variants is sustained by F1 clade, which circulates at high prevalence in South America and Eastern Europe. Aim of this study was to define clade F1 origin, population dynamics and epidemiological networks through phylogenetic approaches. We analyzed pol sequences of 343 patients carrying F1 subtype stored in the ARCA database from 1998 to 2009. Citizenship of patients was as follows: 72.6% Italians, 9.3% South Americans and 7.3% Rumanians. Heterosexuals, Homo-bisexuals, Intravenous Drug Users accounted for 58.1%, 24.0% and 8.8% of patients, respectively. Phylogenetic analysis indicated that 70% of sequences clustered in 27 transmission networks. Two distinct groups were identified; the first clade, encompassing 56 sequences, included all Rumanian patients. The second group involved the remaining clusters and included 10 South American Homo-bisexuals in 9 distinct clusters. Heterosexual modality of infection was significantly associated with the probability to be detected in transmission networks. Heterosexuals were prevalent either among Italians (67.2%) or Rumanians (50%); by contrast, Homo-bisexuals accounted for 71.4% of South Americans. Among patients with resistant strains the proportion of clustering sequences was 57.1%, involving 14 clusters (51.8%). Resistance in clusters tended to be higher in South Americans (28.6%) compared to Italian (17.7%) and Rumanian patients (14.3%). A striking proportion of epidemiological networks could be identified in heterosexuals carrying F1 subtype residing in Italy. Italian Heterosexual males predominated within epidemiological clusters while foreign patients were mainly Heterosexual Rumanians, both males and females, and South American Homo-bisexuals. Tree topology suggested that F1 variant from South America gave rise to the Italian F1 epidemic through multiple introduction events. The contact tracing also revealed an unexpected burden of resistance in epidemiological clusters underlying the need of public interventions to limit the spread of non-B subtypes and transmitted drug resistance.

Background Transmitted drug resistance (TDR) is mainly restricted to individuals carrying B subtype, with low prevalence among non-B subtypes when grouped together. Subtype F1 is the most frequent non-B variant found in subjects living in Italy, allowing a specific assessment of TDR associated with this clade. Methods We analysed pol sequences of HIV-1-positive individuals carrying the F1 variant included in the Antiretroviral Resistance Cohort Analysis database in the 1998-2009 period. Mutations were analysed with the Surveillance Drug Resistance Mutation and the International AIDS Society lists for naive and treated patients, respectively. Results Among 343 HIV-1-infected patients carrying an F1 subtype, resistance was evaluated in a subset of 221 patients whose treatment status was known (169 drug naive and 52 drug experienced). The prevalence of TDR was 15.4% (11.8% for nucleoside/nucleotide reverse transcriptase inhibitors, 6.5% for non-nucleoside reverse transcriptase inhibitors and 7.1% for protease inhibitors). Among the 169 naive patients, 75.1%, 10.1% and 7.1% were Italians, South Americans and Romanians, respectively. Heterosexuals were prevalent among Italians and Romanians, while men who have sex with men were predominant among South Americans. The overall frequency of TDR declined from 21.4% to 7.1% in the 1998-2009 period. Although no statistical difference was detected, the frequency of TDR was higher in South Americans (23.5%) compared with Italian and Romanian naive patients (15% and 8.3%, respectively). Discussion Our study shows a remarkable frequency of TDR in the F1 subtype-infected population. The high prevalence of TDR detected in South American subjects is linked to the homosexual route of infection. However, TDR was considerably high also in Italian subjects harbouring the F1 subtype, deserving careful monitoring.

First isolated in the 1960s methicillin-resistant Staphylococcus aureus (MRSA) has become a leading hospital acquired (HA) pathogen, although community acquired isolates (CA-MRSA) are on the rise, particularly in the USA. Treatment of serious MRSA infections has been based for many years upon the use of glycopeptides, i.e. vancomycin and teicoplanin. Other drugs indicated in particular clinical settings, such as prosthetic valve endocarditis or osteomyelitis, are rifampin, gentamycin, fusidic acid, minocycline, co-trimoxazole, clindamycin. Quinolones and doxycycline may be active on some MRSA isolates, and add some this important clinical setting. In the last few years new anti-MRSA drugs have been registered and patented, expanding therapeutic opportunities, i.e. linezolid, the first oxazolidinone, available both as oral and parenteral formulation in being the most widely used new anti-MRSA agent, quinupristin-dalfopristin, daptomycin, a novel lipopeptide, active on germs both in the replicating and in the resting phase, and tigecycline, the first approved glycylcycline. Other drugs from different classes are in the pipeline and will further enhance in the next few years our therapeutic armamentarium: three glycopeptides, i.e. dalbavancin, telavancin, and oritavancin, two broad spectrum cephalosporins, ceftobiprole and ceftaroline, iclaprim, a diaminopyrimidine, as well as a carbapenem, CS- 023/RO-4908463, and adjuvant therapies such as the monoclonal antibody tefibazumab.

The purpose of our study was to determine whether highly active antiretroviral therapy (HAART) reduces the onset of cervical intraepithelial neoplasia (CIN) in HIV-positive women.The study was designed to assess CIN incidence in a cohort of 101 HIV-positive women and to evaluate its relationship with ongoing antiretroviral therapy. The patients were screened through a combined Pap smear and colposcopic examination on a yearly basis. If any abnormalities were reported, the patients underwent targeted biopsy with histological confirmation of the diagnosis.During the follow-up period, 38 patients (37.6%) developed histologically verified CIN, including low-grade CIN in seven patients (6.9%) and high-grade CIN in 31 patients (30.4%). Over the study period, 43 patients (42.6%) were treated with HAART for at least 6 months, the average duration of treatment being 37 months. Analysis of HAART efficacy in preventing CIN onset, determined by the Cox regression model with a time-dependent covariate adjusted for the CD4 level at the first visit, showed that HAART significantly reduced the risk of developing CIN (hazard ratio, 0.3; p = 0.004).HIV-positive patients present a high incidence of CIN and of high-grade CIN in particular. HAART exhibits a protective action against the onset of cervical lesions.