The management of visceral leishmaniasis (VL) in HIV-infected patients is complex because of high mortality rates, toxic drug-related side effects, and a high risk of treatment failure and relapse. We report a case of active chronic VL in an HIV-1-infected woman presenting multiple secondary VL episodes over 7 years leading to massive splenomegaly and blood transfusion-dependent anemia despite several treatment courses and secondary prophylaxis. The patient was finally successfully treated with rescue treatment based on intravenous pentamidine. Twenty months after discontinuation of pentamidine the patient presented complete clinical and parasitological response. In patients with active chronic VL, treatment with intravenous pentamidine can be effective and should be considered as rescue treatment.

Cutaneous leishmaniasis (CL) has been reported as an emerging concern among international travellers, especially to Central and South America.1 In July 2019, a 42-year-old Italian man with no previous medical history presented to our outpatient clinic due to an ulcerative lesion of the left ear lobe, with concomitant regional lymph nodes enlargement (Figure 1A). The lesion dated back 4 months and was first noted 4 weeks after returning from a touristic travel to Mexico. Histopathology and polymerase chain reaction (PCR) testing on a biopsy specimen confirmed the diagnosis of localized CL, identified as caused by Leishmania mexicana through heat shock protein 70 PCR-restriction fragment length polymorphism. The patient denied fever and other systemic symptoms, PCR for Leishmania spp. was negative on peripheral blood and no sign of mucosal involvement was evidenced during an otorhinolaryngology visit. As ketoconazole is currently not available in Italy and the patient did...

We report the events of an Italian top league soccer club that took place in 1 year (from March 2020 to February 2021) at the time of coronavirus disease 2019 (COVID-19) pandemic. In early March 2020, just before sport competitions were called off due to the national lockdown in Italy, the team, which included 27 players and 26 staff at the time, faced a COVID-19 outbreak, with 16 confirmed and seven probable cases, including three staff members who had to be hospitalised. In May 2020, at the resumption of the training sessions, a high prevalence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G positivity (35/53, 66%) was detected among the members of the group. In the following months, sport activities were organised behind closed doors with stringent risk mitigation procedures in place. As of February 2021, only two new cases of SARS-CoV-2 infection were detected within the group, against more than 3500 nasopharyngeal swabs and 1000 serological tests.

Background and Aims Chronic hepatitis C is the main co-morbidity in adult patients with haemophilia (PwH). It causes progressive liver damage leading to end-stage liver disease and/or hepatocellular carcinoma. Eradication of HCV was possible with interferon (IFN)-based regimens in the past and direct-acting antivirals (DAAs) more recently. PwH have been considered "difficult-to-treat" because of several bad predictors of response. The advent of DAAs has provided high rates of sustained virological response (SVR) despite bad prognostic factors. Here, we present the results of antiviral treatment with DAAs in PwH treated in 2 large Italian Hemophilia Treatment Centers. Methods PwH and chronic hepatitis C sustained by any HCV genotype were eligible for therapy with DAAs, including those with compensated cirrhosis, HIV infection and/or previous failure to IFN-based antiviral therapy. Patients received DAAs for 8-24 weeks according to existing guidelines. SVR was defined as persistent negative serum HCV-RNA at 12 weeks after treatment completion (SVR12). Results Between January 2015 and November 2018, 200 patients aged 21-84 years (median: 50.5) received DAAs. HCV genotype 1 was the most prevalent (158, 79%). Forty patients (20%) were HIV positive, 56 (28%) had cirrhosis and 91 (46%) previously failed interferon-based treatment. Ribavirin was used in 70 (35%). HCV-RNA was undetectable at week 4 in 124/192 (65%) and SVR12 was achieved in 193/195 (99%). No patient had serious side effects related to DAAs. Conclusions DAAs were safe and highly effective in PwH irrespective of HIV status, stage of liver disease severity and/or previous failure to IFN-based therapy.

Current evidence suggests that Polyomavirus (PyV) microRNAs (miRNAs) circulating in biological fluids may be relevant to understanding viral persistence. Here, the expression of polyomavirus BKPyV, JCPyV, MCPyV and SV40 miRNAs in saliva was investigated to evaluate PyV prevalence/persistence in the oral cavity. PyV-DNA status and PyV-miRNA expression was examined in paired saliva and plasma samples of 100 HIV-infected patients and of 50 healthy subjects using digital droplet PCR and PyV-miRNA-5p stem-loop RT-PCR. Overall, the PyV-miRNA in saliva samples showed higher positivity (65%) than PyV-DNA (24%). In particular, the PyV-miRNA prevalence in HIV-infected patients was 66% and that in healthy subjects was 64%. The PyV-DNA prevalence values in the HIV-infected and healthy subjects were 25% and 22%, respectively. The presence of a single type of PyV-miRNA in the saliva of HIV-infected patients ranged from 14% (MCPyV) to 61% (BKPyV) and in healthy subjects ranged from 14% (SV40) to 70% (BKPyV). Moreover, the PyV-miRNA in the saliva of both HIV-infected and healthy subjects exhibited higher prevalence than that in the paired plasma samples. Notably, the saliva of the HIV-infected and healthy subjects was more frequently positive for more than one PyV-miRNA than the paired plasma samples or the PyV-DNA in the paired saliva and plasma samples. Collectively, these data suggest that additional investigations of PyV-miRNA present in saliva may be useful to shed light on their utility as a surrogate for determining viral infection.

Abstract 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.

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population.

s / Digestive and Liver Disease 48S (2016) e1–e17 e5 eGFR was ≥60mL/min/1.73m2 in 92 patients (93.8%) and between45and59mL/min/1.73m2 in6patients (6.1%).Glomerular involvement was found in 19 patients (19.4%), tubular involvement in 31 (31.6%) and they co-occurred in 10 patients (p=0.034). Subjects with glomerular or tubular involvement, or both, showed significantly lower eGFRvalues (p=0.005). AROC curvewasdrafted and a cut point of 90ml/min predicted renal involvement (RI) (sensitivity 63%, specificity 75%), although it was unable to distinguish tubular vs glomerular involvement (p=0.914). Patients with RI were older, had higher ACR and 1MCR levels and exhibited a more severe KDIGO stage. No association was found between RI and: HCV-RNA levels, liver stiffness and liver function tests. L-FABP andKIM-1 levelswere significantlyhigher inpatientswithRI. Tubular involvement was significantly associated with increased levels of L-FABPandKIM-1,while glomerular involvementwas associated only with high L-FABP level. Conclusion: Tubular and/or glomerular involvement are quite frequent in HCV cirrhotic patients. The occurrence of eGFR<90ml/min/1.73m2 allows to suspect renal involvement and should prompt to monitor renal function more closely. http://dx.doi.org/10.1016/j.dld.2015.12.024

The EASL 2015 Guidelines considers HIV co-infection as an HCV treatment priority.

We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements.

BACKGROUND:In light of their regulatory role, changes in the expression of Polyomavirus JC (JCPyV) microRNAs may be relevant for virus reactivation and the development of progressive multifocal leukoencephalopathy (PML). OBJECTIVES:To investigate the presence of JCPyV-DNA and JCPyV microRNA expression in clinical specimens of patients at risk for PML. STUDY DESIGN:The JCPyV-DNA and microRNA status was assessed in peripheral blood mononuclear cells (PBMCs) and plasma from 100 HIV patients, in serum and cerebrospinal fluid (CSF) from 14 HIV PML patients and in PBMCs and plasma from 50 healthy controls using Multiplex real-time PCR and JCPyV miRNA-J1-3p and -5p stem-loop RT-PCR. The JCPyV-DNA microRNA-expressing region was also sequenced. RESULTS:A positive JCPyV-DNA status was more prevalent in HIV patients (67%, 67/100) compared to healthy controls (18%, 9/50). Among these, 46% and 42% of the HIV patients and 18% and 0% of the healthy controls were positive based on PBMC and plasma determinations, respectively. PBMC JCPyV microRNA positivity was observed in 22 out of 46 (48%) JCPyV+ HIV patients and in 3 out of 9 (33%) JCPyV+ healthy controls. Moreover, JCPyV microRNAs in exosomes were found in 6 out of 100 (6%) HIV plasma samples, in 12 out of 50 (24%) healthy samples, in 6 out of 14 (43%) serum samples, and in 3 out of 5 (60%) HIV PML CSF samples. Of note, the JCPyV-DNA load was inversely correlated with expression of the viral microRNA. The JCPyV microRNA genomic expression region showed a different combination of three mutations. CONCLUSIONS:The low levels of JCPyV microRNA expression in HIV patients with high JCPyV-DNA prevalence observed in this study highlight the potential clinical relevance of JCPyV microRNAs in PML risk assessment.

Chronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10-25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0-6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).

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We assessed hand hygiene adherence in 2 infectious disease units. In one unit, adherence declined slightly from year 1 (84.2%) to year 4 (71.0%) after a multimodal intervention but remained much higher than before intervention. Adherence dropped in the second unit after a loss of leadership (from 50.7% to 5.7%). Strong leadership presence may improve hand hygiene adherence.

BACKGROUND:We assessed the virological response of DRV/r-based dual therapy in drug-experienced patients included in the Italian antiretroviral resistance database (ARCA).MATERIALS AND METHODS:Patients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow-up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point.RESULTS:Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5-13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow-up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By regimen, patients treated with DRV/r-RAL showed a non-significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40-0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001).CONCLUSIONS:Among experienced patients, the best candidates to dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.

Background Recent reports show a correlation between haemophilia and bone mineral density reduction. HIV, HCV and their treatments are independently associated to an increased risk of osteoporosis. A pivotal role in bone mineralization is played by Vitamin D. Objectives This study compares Vitamin D level, bone metabolism markers and bone mineral density (BMD) in haemophiliacs with or without co-infections. Methods 78 adult patients with severe or moderate haemophilia A or B and HIV and/or HCV infection were studied. BMD was measured by dual energy X-ray absorptiometry (DeXA) at femoral area (F) and lumbar spine (L) and was correlated to laboratory values and haemophilic arthropathy assessed using the World Federation of Haemophilia orthopaedic joint scale (WFH score) and the radiological Pettersson score. Results DeXA showed a homogeneous F-BMD reduction of a part from the belonging group, while L-BMD was significantly lower in pts with HIV and HCV infection (p<0.05). The WFH score was higher in pts with HIV and HCV infection (p<0.002) and in pts with HCV infection (p<0.006). The radiological score was higher in pts with HCV infection than in the other pts (p<0.001). Overall 25-hydroxyvitamin D was reduced in 87% of patients, in particular in 100% of pts with HIV and HCV, 73% of pts with HCV infection and 88% of un-infected subjects. Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in all pts (p<0.001 and p<0.01). Conclusions The worse clinical and radiological scores in patients with infections are most likely related to the amount of patients with more severe coagulopathy in those groups. A high prevalence of hypovitaminosis D has been found in haemophiliacs, a part from the belonging group. The homogeneous F-BMD reduction could be explained by the pivotal role of arthropathy; the lower L-BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest the faster bone metabolism in case of infections. Disclosure of Interest None Declared

HaemophiliaVolume 19, Issue 5 p. e316-e318 Letter to the Editor Are the standard definitions of osteopenia and osteoporosis appropriate for coinfected patients with haemophilia? S. Linari, S. Linari Agency for Haemophilia, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorG. Montorzi, G. Montorzi Agency for Haemophilia, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorM. Borderi, M. Borderi Infectious Diseases Unit, University Hospital of Bologna, Bologna, ItalySearch for more papers by this authorD. Bartolozzi, D. Bartolozzi Infectious Diseases Unit, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorD. Melchiorre, D. Melchiorre Department of Bio-Medicine, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorM. Morfini, Corresponding Author M. Morfini Agency for Haemophilia, University Hospital of Firenze, Firenze, Italy Correspondence: Dr Massimo Morfini, Agency for Haemophilia, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, Firenze, Italy. Tel.: +39 055 7947587; fax: +39 055 7947794; e-mail: [email protected]Search for more papers by this author S. Linari, S. Linari Agency for Haemophilia, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorG. Montorzi, G. Montorzi Agency for Haemophilia, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorM. Borderi, M. Borderi Infectious Diseases Unit, University Hospital of Bologna, Bologna, ItalySearch for more papers by this authorD. Bartolozzi, D. Bartolozzi Infectious Diseases Unit, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorD. Melchiorre, D. Melchiorre Department of Bio-Medicine, University Hospital of Firenze, Firenze, ItalySearch for more papers by this authorM. Morfini, Corresponding Author M. Morfini Agency for Haemophilia, University Hospital of Firenze, Firenze, Italy Correspondence: Dr Massimo Morfini, Agency for Haemophilia, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, Firenze, Italy. Tel.: +39 055 7947587; fax: +39 055 7947794; e-mail: [email protected]Search for more papers by this author First published: 19 June 2013 https://doi.org/10.1111/hae.12207Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Linari S, Montorzi G, Bartolozzi D et al. Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients. Haemophilia 2013; 19: 126–33. 2Baim S, Binkley N, Bilezikian JP et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 2008; 11: 75–91. 3Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20: 2165–74. 4Gibellini D, Borderi M, De Crignis E et al. Analysis of the effects of specific protease inhibitors on OPG/RANKL Regulation in an osteoblast-like cell line. New Microbiol 2010; 33: 109–15. 5Mora S, Zamproni I, Cafarelli L et al. Alterations in circulating osteoimmune factors maybe responsible for high bone resorption rate in HIV-infected children and adolescents. AIDS 2007; 21: 1129–35. 6Glesby MJ. Bone disorders in human immunodeficiency virus infection. Clin Infect Dis 2003; 37(Suppl 2): S91–5. 7Negredo E, Bonjoch A, Gomez-Mateu M et al. Time of progression to osteopenia/osteoporosis in chronically HIV-infected patients: screening DXA Scan. PLoS ONE 2012; 7(10): e46031. 8Anagnostis P, Vakalopoulou S, Slavakis A et al. Reduced bone mineral density in patients with haemophilia A and B in Northern Greece. Thromb Haemost 2012; 107: 545–51. Volume19, Issue5September 2013Pages e316-e318 ReferencesRelatedInformation