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Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19., Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days., Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%)., Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug., Competing Interests: Declaration of Competing Interests None., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: chronic viral infections by both HCV and HIV may lead to polyclonal activation of B cells resulting in hypergammaglobulinemia. This study retrospectively analyzed the effect of HCV eradication with interferon-free direct-acting antiviral agents (DAAs) on the gamma globulin levels in HCV-infected patients with or without HIV coinfection to identify factors potentially associated with gamma globulins decrease., Methods: The charts of patients treated with DAAs for HCV chronic infection between January 2015-June 2019 were retrospectively reviewed. Gamma globulin levels before treatment and 12 weeks after the end of anti-HCV therapy were evaluated along with liver tests, liver fibrosis stage by elastography, SVR achievement, HIV-coinfection. Multivariate analyses were carried out to assess the factors and the potential confounders related to the changes in gamma globulin levels., Results: A significant decrease of gamma globulin concentration was found in both cirrhotic and non-cirrhotic HCV-infected patients after treatment (from mean ± SD of 1.5 ± 0.44 g/dL to 1.31 ± 0.37 g/dL; p = 0.0001). Adjusted linear regression analyses of serum gamma globulin changes from baseline to SVR12 showed a positive significant association with pre-treatment gamma-globulin levels (β-coefficient -0.23; p = 0.0001), Metavir fibrosis score (β-coefficient -0.74; p = 0.008), ALT values and baseline HCV-RNA levels > 800,000. No difference was found between HIV-infected and HIV-uninfected patients., Conclusions: Our study confirms previous preliminary observation of the decrease of serum gamma globulins after HCV eradication either achieved with interferon-based therapy or with DAAs, suggesting a leading role of the virus on the activation of B cell compartment and gamma globulins production., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Late diagnoses are still a cause of increased HIV-related morbidity and mortality despite the availability of highly effective treatments. The aim of this study was to identify indicator conditions (ICs) in late presenters with HIV infection (LPs) that may represent missed opportunities of undertaking earlier HIV testing., Methods: The medical records of LPs referred to a specialist clinic in Milan, Italy, between 2011 and 2017 were reviewed to assess the frequency of ICs during the five years preceding diagnosis. Logistic regression analysis was used to investigate the factors associated with missed opportunities of making an earlier diagnosis., Results: The analysis considered 203 LPs (60.6% of the patients newly diagnosed as having HIV infection during the study period). Most had had ≥1 medical encounter in the five years before diagnosis, and 54 (26.6%) had been diagnosed as having ≥1 IC without undergoing HIV testing. The most frequent ICs were herpes zoster (19.8%), constitutional symptoms (17.4%) and lympho/thrombocytopenia (12.8%), and the missed opportunities for testing occurred in the settings of primary care (44.9%), specialist medical (38.2%) or surgical services (11.3%), and emergency departments (5.6%). Twenty-five (53.2%) of the 47 subjects with a non AIDS-defining IC had AIDS at the time of the diagnosis of HIV infection. Subjects aged >60 years were at increased risk of missed diagnostic opportunities (aOR 4.80, p = 0.008)., Conclusion: Implementing IC-guided HIV testing in non-specialist settings is an essential means of reducing late diagnoses of HIV infection even in the case of older subjects., Competing Interests: Declaration of Competing Interest SR declares participation to advisory boards, CME activities and research grants from BMS, MSD, Janssen, Gilead and ViiV/GSK. AG has received consultancy payments from Mylan. MG has received research grants, consultancy payments and speaker's fees from Bristol-Myers-Squibb, Gilead, ViiV/GSK, Merck Sharp Dohme, ABBvie, Janssen and Roche. The authors report no other conflicts of interest in this work., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Dengue fever is a mosquito-borne infection that co-circulates with Chikungunya and Zika virus infection in many parts of the world. Dengue virus (DENV) is occasionally responsible for acute hepatitis and a few cases of acute hepatitis due to co-infection with DENV and hepatitis E virus have been described in India. A 37-year-old Cuban woman living in Italy was admitted to our hospital with a presumed arboviral infection upon her return to Italy short after a 15-day trip to her home-country to visit relatives. An acute infection due to DENV serotype 1 was initially diagnosed, following a clinical course characterized by signs of liver dysfunction that were possibly due to co-infection with hepatitis E virus.

Background: As HIV-infected patients aged 50 years or older are at increased risk of comorbidities and multidrug treatments, we examined their exposure to the potential drug-drug interactions (PDDIs) of antiretroviral (ARV) and other medications., Methods: This cross-sectional study involved the patients aged 50 years or older receiving ARV and non-ARV medications at our clinic. PDDIs were identified using the University of Liverpool HIV Drug Interaction Checker. Logistic regression models were used to assess risk factors for PDDIs. The American Geriatrics Society Beers Criteria were used to identify potentially inappropriate medications (PIMs)., Results: A total of 395 (53.9%) of 744 patients showed ≥1 PDDI: 47.4% ≥ 1 amber-PDDI (comedications requiring appropriate management) and 5.6% ≥ 1 red-PDDI (contraindicated comedications). A higher risk of PDDIs was associated with the use of ≥5 medications (P < 0.001), of antiosteoporotics (P < 0.001), calcium channel blockers (P < 0.001), anti-benign prostatic hypertrophy agents (P < 0.001), hypnotics/sedatives (P = 0.022), and anticoagulants (P = 0.006). A higher risk of red-PDDIs was associated with the use of antacids (P < 0.001), anti-benign prostatic hypertrophy agents (P < 0.001) and antipsychotics (P = 0.023). The use of nucleoside reverse transcriptase inhibitor + nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor rather than protease inhibitor-based regimens was associated with a reduced risk of PDDIs (P < 0.001). Overall, 119 (16.0%) patients were receiving PIMs (mainly hypnotics/sedatives) and 49 (41.2%) of them had PDDIs able to increase the blood levels of these medications., Conclusions: Older patients with HIV are highly exposed to PDDIs between ARVs and comedications. The knowledge of their complete medication regimens and the screening for PDDIs and PIMs is therefore crucial to prevent drug-related adverse outcomes in this population.

Background: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study., Methods: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events., Results: 953 HIV-HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4 + T-cell count <350 cells/mm 3 decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir., Conclusions: Although use of tenofovir-based cART among HIV-HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.

Background: Onchocerciasis is endemic in a number of tropical countries in Africa and South America, and it is occasionally diagnosed as an imported disease in non-endemic areas., Methods: We describe the case of an African migrant with long-lasting pruritus and a cutaneous nodule who was diagnosed with onchocerciasis after nodulectomy, and review the medical literature regarding imported cases of onchocerciasis in the period 1994-2014., Results: Twenty-nine cases of onchocerciasis diagnosed in migrants from endemic countries, and in expatriates and travellers from non-endemic areas were retrieved. They were predominantly males (73.3%), had a median age of 37 years (two were aged <15 years), and acquired the diseases in sub-Saharan Africa, most frequently in Cameroon (43.3%). Diagnosis of onchocercosis was proven in 73.3% of patients. The most frequent clinical manifestations in these and our own patient were pruritus (23/30, 76.7%), unilateral leg or forearm swelling (13/30, 43.3%) and rash (12/30, 40.0%), whereas only two (6.9%) complained of eye symptoms. Eosinophilia was observed in almost all of the patients (92.0%), with median counts of 2915/μL among migrants and 1960/μL among travellers/expatriates. Eighteen patients underwent a skin snip biopsy, which was positive in 10 cases (55.5%); in the other 13 patients the parasite was directly demonstrated by means of a skin or nodule biopsy (n = 5), nodulectomy (n = 5) or slit lamp examination (n = 3). Eighteen received ivermectin, alone, and seven ivermectin combined with diethylcarbamazine or doxycycline. Outcome details were available for only 14 patients, all of whom were asymptomatic after a median follow-up of 10 months (range 1-48)., Conclusions: Onchocerciasis is a neglected tropical disease whose subtle and non-specific features may lead to under-diagnosis or underreporting in non-endemic areas. Physicians should consider this tropical disease when caring for migrants and travellers/expatriates with pruritus, skin lesions and eosinophilia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We evaluated predictive factors involved in durability and therapeutic failure of atazanavir (ATV)-based antiretroviral regimens with or without ritonavir (r) in real life setting. This retrospective study of HIV-1-positive patients evaluated the factors related to ATV continuance and the time-dependent probability of therapeutic failure (HIV-RNA >200 copies/mL and concomitant discontinuation of ATV). We also investigated the rate of therapeutic failure and the variations in total bilirubin levels from starting unboosted ATV-based regimens. The study involved 1030 patients: 183 treatment-naïve patients (17.8%) started ATV/r (17 subsequently switched to unboosted ATV); 653 (63.4%) switched to ATV/r from previous antiretroviral regimens (121 subsequently switched to unboosted ATV); and 194 (18.8%) switched to unboosted ATV from previous ATV-free regimens. The median ATV follow-up was 28 months (interquartile range 7-56). The risk of ATV discontinuation was significantly lower in patients switched to unboosted ATV from ATV/r (HR 0.45; p < 0.0001). The discontinuation of ATV correlated with female gender (HR 1.26; p = 0.035), use of a zidovudine/didanosine/stavudine containing backbone (HR 1.8; p = 0.004), and a baseline CD4+ cell counts of <200/μL (HR 1.54; p = 0.003), the last of which was also associated with a higher risk of therapeutic failure (HR 2.42; p = 0.001). Total bilirubin levels were significantly lower in the patients switching from ATV/r to unboosted ATV. Unboosted ATV-based therapies are safe and effective options in patients whose immuno-virological conditions are stable, and allow the long-term survival of ATV-containing regimens., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The incidence of non-AIDS-defining cancers (NADCs) in HIV-positive patients has increased over recent years. Most studies of the risk and spectrum of NADCs are primarily based on male populations, and only a few have provided specific information regarding females., Methods: We retrospectively analyzed all incident NADCs occurring in a cohort of HIV-positive patients followed up between 1985 and 2011. Incidence rates before and after the introduction of highly active antiretroviral therapy (HAART) were examined using Poisson regression models. Standardized incidence ratios (SIRs) were used to compare the cancer risk of HIV-infected subjects with that of the age- and gender-matched general population as estimated by the Milan Cancer Registry., Results: Five thousand nine hundred twenty-four patients (4382 men and 1542 women) contributed 50,990 person-years to the follow-up. Among them, 144 had new NADC diagnosis. The overall incidence increased from 1.0 case/1000 person-years in the pre-HAART period to 4.5 cases/1000 person-years in the HAART period (P < 0.01). In women, the risks were higher than expected in the case of cancer of the vulva (SIR = 69.2), Hodgkin lymphoma (SIR = 7.5), anal cancer (SIR = 41.2), and lung cancer (SIR = 4.8). In men, the risks were higher than expected in the case of anal cancer (SIR = 91.5), Hodgkin lymphoma (SIR = 13.0), tonsil cancer (SIR = 10.9), lung cancer (SIR = 2.1), and liver cancer (SIR = 7.1)., Conclusions: The spectrum and incidence of NADCs in our cohort increased over time. The incidence of NADCs, especially virus- and smoking-associated cancers, was significantly higher than expected in HIV-positive men and women.

We describe 2 human immunodeficiency virus-infected patients who developed hypertension and severe neurological abnormalities while receiving successful antiretroviral therapy. Neuroimaging findings were characteristic of reversible posterior leukoencephalopathy syndrome, a brain-capillary leak syndrome with hypertension and endothelial damage. We discuss the role of antiretroviral therapy-associated metabolic alterations in endothelial damage, hypertension, and reversible posterior leukoencephalopathy syndrome.