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Purpose: Besides the well-established efficacy in preventing severe COVID-19, the impact of early treatments, namely antivirals and monoclonal antibodies (mAbs), on the time length to negativization of SARS-CoV-2 nasal swabs is still unclear. The aim of this study was to compare the efficacy of different early treatments in reducing the SARS-CoV-2 viral shedding, identifying a single drug that might potentially lead to a more rapid negativization of SARS-CoV-2 nasal swab., Methods: This was a single-centre, retrospective, observational study conducted at Ospedale Luigi Sacco in Milan. Data of high-risk COVID-19 patients who received early treatments between 23 December 2021 and March 2023 were extracted. The comparison across treatments was conducted using the Kruskall-Wallis test for continuous variables. Dunn's test with Bonferroni adjustment was performed for post-hoc comparisons of days to negativization. Secondly, a negative binomial regression adjusted for age, sex, number of comorbidities, immunosuppression, and SARS-CoV-2 vaccination status was implemented., Results: Data from 428 patients receiving early treatments were collected. The majority were treated with Nirmatrelvir/Ritonavir and were affected by SARS-CoV-2 Omicron infection with BA.2 sublineage. The median length time to SARS-CoV-2 nasal swab negativization was 9 days [IQR 7-13 days]. We found that Nirmatrelvir/Ritonavir determined a significant decrease of the length time to SARS-CoV-2 nasal swab negativization compared to mAbs (p = 0.003), but not compared to Remdesivir (p = 0.147) and Molnupiravir (p = 0.156)., Conclusion: Our findings highlight the importance of promptly treating high-risk COVID-19 patients with Nirmatrelvir/Ritonavir, as it also contributes to achieving a faster time to negative SARS-CoV-2 nasal swabs., (© 2024. The Author(s).)

Background and Objectives: Liver transplantation is now considered a safe procedure in patients with HIV because of the advent of potent antiretroviral therapies (ART)., Objective: We aimed to describe the use of dolutegravir-based maintenance ART in patients with HIV and liver transplant regularly followed in our hospital., Methods: We searched the database of our Department of Infectious Diseases for liver transplant recipients receiving calcineurin inhibitor-based maintenance immunosuppression concomitantly treated with dolutegravir for at least 1 month., Results: Ten HIV-positive liver transplant recipients were identified. At 4.6 ± 3.5 years post-transplant, all the patients were switched to dolutegravir-based therapies for treatment simplification. However, at 1 year after the switch, five of the ten patients returned to their previous ART regimens because of increased serum transaminases (n = 1), reversible increased serum creatinine (n = 4), repeated episodes of nausea/vomiting (n = 1) and variable out-of-range concentrations of tacrolimus or cyclosporine (n = 2). However, it should be recognized that these events cannot be unequivocally ascribed to dolutegravir and, in the case of increased serum creatinine, are predictable., Conclusions: The management of HIV-positive liver transplant recipients in clinical practice is a complex task, where possibility of simplifying antiretroviral regimens must be balanced with the need to guarantee optimal immunosuppression and the finest treatment tolerability. A multidisciplinary approach involving physicians and clinical pharmacologists/pharmacists could help achieve this goal.

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.)

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and InnovationsHCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs).HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8-12 weeksConventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Background: Gastrointestinal basidiobolomycosis (GIB) is a rare mycosis affecting almost exclusively immunocompetent subjects., Methods: We describe a case of GIB caused by Basidiobolus ranarum in a 25-year-old Italian immunocompetent man resident in Ireland who presented a 2-month history of epigastric pain. Suspecting colon cancer he underwent a right hemicolectomy subsequently leading to a diagnosis of GIB by means of molecular biology. After surgery a 9-month therapy with itraconazole was employed with a good outcome. A review of medical literature regarding GIB cases published in the period 1964-2017 is presented., Results: One-hundred and two cases of GIB were included in this analysis. The disease was observed predominantly in male gender (74.5%) and children (41.2%). Abdominal pain was the single most common complaint (86.3%) followed by fever (40.2%) and evidence of an abdominal mass (30.4%). Peripheral blood eosinophilia was detected in 85.7% of cases. Most of the patients were diagnosed in Saudi Arabia (37.2%) followed by USA (21.6%) and Iran (20.6%). Surgery plus antifungal therapy was employed in the majority of patients (77.5%). An unfavourable outcome was documented globally in 18.6% of patients., Conclusions: GIB seems to be an emerging intestinal mycosis among immunocompetent patients living in the Middle East and Arizona., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Changes in the incidence, clinical features and microbiology of infective endocarditis (IE) observed in a single center in Italy were compared between the period 2003-2010 and 2011-2015., Methods: All cases of IE, defined as definite or possible according to the modified Duke criteria, observed at the 'L. Sacco' Hospital in Milan, Italy between 2003 and 2015 were retrospectively reviewed., Results: 366 episodes of IE were identified in 325 patients. The mean number of incident IE over the period 2003-2015 was 1.43 (range: 0.6-2.1) cases per 1000 admissions, with a significantly increasing trend from a mean of 1.28-1.72 cases per 1000 admissions/year in 2003-2010 and 2011-2015, respectively (+34%; p = .04). Staphylococci remain the leading pathogens causing IE (29%) with a relative increase of methicillin-resistant Staphylococcus aureus between the two periods. Streptococci and enterococci account for 26% and 18% of IE, respectively. We found an increase in the proportion of cases due to enterococci (from 14% in 2003-2010 to 22% in 2011-2015). The rate of in-hospital mortality was 19%, similar in the two periods studied., Conclusion: The incidence of IE continuously increased in our cohort over the past decade and, along with the aging of the population, a raise in the incidence of health care-associated infections and a change in the distribution of prevalent pathogens were observed. Surgery was independently associated with higher in-hospital survival (AOR, 95% CI: 0.38, 0.19-0.74; p = .005). A constant surveillance is required to guide the optimal management of the changing epidemiology of IE.

The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless, it has not established so far whether HCV treatment with new direct acting agents could impact on estimated glomerular filtration rate (eGFR) variations. In the present work, we examined the real-life data on renal function that have been prospectively collected in the SIMIT compassionate-use program of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage C, with median age of 52 years (48.0-56.5) and median liver stiffness of 7.8 kPa (6.7-9.2). Median baseline eGFR was 102.0 (90.8-108.1), changing to 99.8 (83.5-104.8) at the end of treatment (EoT), and 100.0 (87.3-105.6) 12 weeks after the EoT (FU12), p<0.0001. No patient had grade 3-4 increase of creatinine. At EoT 60/144 (41.7%) patients had ≥ 5% reduction in their eGFR, confirmed at FU12 in 39/60 (65.0%) cases. Longer duration of HCV infection (cut-off 12.9 years), lower HCV-RNA viral load (cut-off 1,970,160 IU/ml) and lower platelet count (cut-off 167,000 x106/L) were significantly associated with eGFR decline at logistic analysis (adjOR 2.9, 95%CI 1.0-8.8, p = 0.05; adjOR 3.5, 95%CI 1.2-10.4, p = 0.02; adjOR 2.8, 95%CI 1.1-6.8, p = 0.03, respectively). After repeating the analysis throughout a mixed model, a higher eGFR decline was highlighted in patients concomitantly treated with tenofovir (p = 0.0001), ribavirin (p = 0.0001), or integrase inhibitors (p <0.0001), with longer duration of HIV (p = 0.0002) and HCV infection (p = 0.035), lower baseline HCV RNA (p <0.0001), previous HCV treatment (p<0.0001), and older age (p<0.0001). In conclusion, our study confirms a good renal safety profile of OBV/PTV/r + DSV treatment in HIV/HCV patients, and the median decline of 2 ml/min in eGFR, albeit statistically significant, is of doubtful clinical significance. The role of aging, concomitant therapies and duration of HIV/HCV infection needs to be further investigated.

Objective: Few real-life data are available on the retreatment of patients who failed direct-acting antiviral (DAA)-regimens. We reported the outcome of retreatment with approved DAA regimens in a real-life cohort of patients who previously failed an all-oral DAAs combination and we analyzed the association with resistance substitutions (RASs) performed at the time of virological failure., Aim and Methods: Next-generation sequencing of the NS3, NS5A, and NS5B regions was performed by Illumina deep sequencing. The sequence reads were analyzed by an in-house pipeline., Results: Of the 16/759 (2%) patients who failed to achieve a sustained virological response at 12 weeks to all-oral DAAs from December 2014 to January 2016, 10 were retreated with licensed DAAs regimens. In all the patients, retreatment was followed by sustained virological response at 12 weeks. Baseline NS3-RASs before retreatment were observed in two patients who failed a sofosbuvir/simeprevir regimen: D168V RAS was detected in a genotype-4 patient, whereas the complex RAS-pattern Q80K, I170V, R155K, D168E was observed in a genotype-1a patient. Only one of the two patients who previously failed ombitasvir, paritaprevir/ritonavir, and dasabuvir underwent RAS analysis at relapse and showed baseline NS5A RAS (M28V) before retreatment., Conclusion: These real-life findings indicated a high efficacy of sofosbuvir+NS5A-inihbitors in retreating NS3-experienced patients and also NS5A-experienced patients by using a 24-week course ribavirin-containing regimen. The relevance of hepatitis C virus resistance testing before retreatment remains to be better defined to guide the choice of the new regimen before retreatment in DAA-experienced patients.

Objectives: Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations., Methods: The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations., Results: A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed., Conclusions: HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Here we describe the case of a HIV-positive patient with acute hepatitis C virus reinfection, who was successfully treated with an interferon-free regimen of ledipasvir/sofosbuvir.

Objectives: To investigate the clinical and laboratory patterns of HCV-unrelated cryoglobulinaemic vasculitis (CV), and the factors influencing its outcome., Methods: Prospective study of all anti-HCV and HCV-RNA negative patients with CV who have been observed since January 2004 in 17 centres participating in the Italian Group for the Study of Cryoglobulinaemias (GISC)., Results: 175 enrolled were followed up for 677 person-years. The associated conditions were primary Sjögren's syndrome (21.1%), SLE (10.9%), other autoimmune disorders (10.9%), lymphoproliferative diseases (6.8%), solid tumours (2.3%) and HBsAg positivity (8.6%), whereas 69 patients (39.4%) had essential CV. There were significant differences in age (p<0.001), gender (p=0.002), the presence of purpura (p=0.005), arthralgia (p=0.009), liver abnormalities (p<0.001), sicca syndrome (p<0.001), lymphadenopathy (p=0.003), splenomegaly (p=0.002), and rheumatoid factor titres (p<0.001) among these groups. Type II mixed cryoglobulins were present in 96 cases (54.9%) and were independently associated with purpura and fatigue (odds ratio [OR]4.3; 95% confidence interval [CI] 1.8-10.2; p=0.001; and OR2.8; 95%CI 1.3-6.3; p=0.012). Thirty-one patients died during follow-up, a mortality rate of 46/1000 person-years. Older age (for each additional year, adjusted hazard ratio [aHR] 1.13; 95%CI 1.06-1.20; p<0.001), male gender (aHR 3.45; 95%CI 1.27-9.40; p=0.015), type II MCG (aHR 3.31; 95%CI 0.09-1.38; p=0.047) and HBsAg positivity (aHR 7.84; 95%CI 1.20-36.04; p=0.008) were independently associated with greater mortality., Conclusions: HCV-unrelated CV is a multifaceted and often disabling disorder. The associated conditions influence its clinical severity, giving rise to significantly different clinical and laboratory profiles and outcomes.

The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono-infected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV mono-infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real-time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P<.01) that was not significantly different between the two study groups. Moreover, a significant decline in estimated glomerular filtration rate (eGFR) was observed from baseline (P<.01), and it was significantly greater in HBV mono-infected than co-infected patients (P=.03). The distribution of ABCC2, ABCC4 and ABCC10 genotypes among a subgroup of 34 patients did not show significant association with eGFR decline <90 mL/min per 1.73 m 2 . Although our findings showed a statistically significant decrease in eGFR with long-term use of TDF, its clinical impact seems to be modest. The role of genetic factors to identify patients at greater risk for developing tenofovir-induced renal toxicity needs to be further investigated., (© 2016 John Wiley & Sons Australia, Ltd.)

Candidemia and invasive candidiasis are major causes of morbidity and mortality, and their incidence is increasing because of the growing complexity of patients. Five species of Candida (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei) account for more than 90% of all diagnosed cases, but their relative frequency varies depending on the population involved, geographical region, previous anti-fungal exposure, and patient age. The best evidence regarding the anti-fungal treatment for invasive candidiasis comes from randomized controlled trials in which more than 85% of the recruited patients had candidemia. In the case of less frequent forms of invasive candidiasis, the recommendations are based on retrospective studies, meta-analyses (when available) and experts' opinions. A pre-emptive approach based on biomarkers and clinical rules is recommended because of the high rate of infection-related mortality among critically ill patients., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: Liver transplantation (LTx) is considered a safe procedure in selected HIV-infected patients. In this clinical setting raltegravir is the antiretroviral of choice due to its optimal tolerability and its negligible interactions with immunosuppressive drugs. We aimed at providing data on the pharmacokinetics of raltegravir in LTx recipients, on which the available information is inconclusive., Methods: In this retrospective multicentre study we characterized the pharmacokinetics of raltegravir in a consecutive series of HIV-infected LTx recipients referred to our laboratory for therapeutic drug monitoring (TDM) and compared the obtained profiles with those collected from a control group of HIV-infected patients., Results: Seventeen HIV-infected LTx patients were considered. LTx recipients had significantly higher raltegravir AUC0-12 compared with the control group of HIV-infected patients [14 314 (11 627-19 998) versus 8795 (5218-12 954) ng·h/mL; P < 0.01]. Two LTx patients experienced moderate increments in serum transaminases, nausea and vomiting that improved after raltegravir dose reduction., Conclusions: High raltegravir exposure and acceptable safety profile were observed in HIV-infected LTx recipients. Our results highlight that some patients may obtain an advantage from TDM-guided raltegravir dose adjustments with potential benefits in terms of drug tolerability., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Fungal endocarditis (FE) is a "modern" disease that is considered an emerging cause of infective endocarditis (IE). The most frequently identified fungal pathogens are Candida spp., which are responsible for up to two-thirds of all cases; the remaining cases are due to Aspergillus spp., Histoplasma capsulatum or, more rarely, other yeasts and moulds., Objectives: To describe the prevalence, clinical characteristics and outcome of FE diagnosed in a single tertiary centre and review the literature concerning FE., Design and Setting: An 8-year retrospective review of the case records of patients attending a single Italian University Centre and diagnosed as having definite or probable IE as defined by the modified Duke criteria., Results: Six patients were identified from 229 episodes of IE: five cases involved a prosthetic valve, and one a native valve of an intravenous drug user. Five cases were caused by Candida spp. (two by C. albicans, one each by C. lusitaniae, C. dubliniensis and C. glabrata) and one by Aspergillus flavus. Three patients were treated by means of surgery plus antifungal therapy; two received antifungal therapy alone. Three patients survived, but only the patient with Aspergillus endocarditis was followed up for a long time., Conclusions: FE is difficult to diagnose but generally associated with healthcare infections. The optimal treatment is poorly characterised, and international collaborative studies are urgently needed to evaluate newer antifungal agents.

Mixed cryoglobulinaemia syndrome (MCS) is associated with a number of infectious, autoimmune and lymphoproliferative disorders, particularly chronic hepatitis C infection. Although circulating mixed cryoglobulins (cMCGs) are a frequent finding in HCV-infected patients, only a minority of them develop a frank MCS. The only available data concerning the prevalence of MCS, which is generally considered a rare disease, come from hospital records. The aim of this investigation was to estimate the prevalence of cMCGs and MCS in a population-based study. All of the adult residents in Origgio, a town of about seven thousand inhabitants in northern Italy, were mailed a validated questionnaire, and a randomly selected sample of respondents was invited to undergo a clinical examination and laboratory tests including the determination of cMCGs. The 1594 respondents to the questionnaire (54.3% women, 64.5% aged >49years) accounted for 26.4% of the total adult population. Forty-nine (3.1%) positively responded to at least two questions, including a disproportionately high number of people aged >70years (p=0.001). Of the 266 randomly selected subjects invited to undergo a clinical examination and laboratory tests, 147 accepted, 30 (20.4%) of whom had asymptomatic type III cMCGs and four MCS. The risk of cMCG positivity was independently associated with C4 levels of <16mg/dL (adjusted odds ratio [AOR] 4.40, 95% confidence interval [CI] 1.07-18.08; p=0.040) and HCV positivity (AOR 6.87, 95% CI 1.16-40.79; p=0.034). No co-morbidities known to be related to cMCG production could be detected in more than 50% of the positive cases. After including the other positive respondents who agreed to undergo a clinical examination, the number of diagnosed MCS increased to seven: five HCV-related, one HBV-related, and one essential MCS. In conclusion, MCS seems to be more frequent than expected for a 'rare' disease, and the unexpectedly high prevalence of cMCGs raises questions about the frequency with which they are triggered, the spectrum of diseases involved in triggering them, and their real role as disease indicators., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: To describe the pathogenesis, clinical presentation, cerebrospinal fluid findings and outcome of Aspergillus meningitis, meningoencephalitis and arachnoiditis., Methods: A case of Aspergillus meningitis is described. A comprehensive review of the English-language literature was conducted to identify all reported cases of Aspergillus meningitis described between January 1973 and December 2011., Results: Ninety-three cases (including the one described herein) of Aspergillus meningitis were identified. Fifty-two (55.9%) were in individuals without any predisposing factor or known causes of immunosuppression. Acute and chronic meningitis was diagnosed in 65.6% of patients and meningoencephalitis in 24.7% of them with the remaining presenting with spinal arachnoiditis and ventriculitis. Cerebrospinal fluid cultures for Aspergillus spp. were positive in about 31% of cases and the galactomannan antigen test in 87%. Diagnosis during life was achieved in 52 patients (55.9%) with a case fatality rate of 50%. The overall case fatality rate was 72.1%., Conclusions: Aspergillus meningitis may occur in both immunocompetent and immunocompromised patients and run an acute or chronic course. The findings of this systematic review extend the information on this life-threatening infection and could assist physicians in achieving an improved outcome., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

The aim of this randomised, prospective, open-label, multicentre pilot clinical trial was to compare the 48-week toxicity profile of lopinavir/ritonavir (LPV/r) monotherapy with LPV/r-based HAART (KaMon = Kaletra monotherapy) in HIV/HCV patients undergoing HCV treatment. The study involved 30 HIV/HCV co-infected patients naive to anti- HCV therapy. One patient in each arm (6.7%) discontinued anti-HCV therapy because of adverse events. There were no significant between-group differences in terms of the proportion of patients experiencing AEs (p=0.999) or the number of grade 3-4 AEs (p=0.146). No HIV failure was observed. The safety profile of LPV/r monotherapy was similar to that of LPV/r-based HAART, thus encouraging HAART simplification in patients receiving anti-HCV treatment.

Objective: The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion., Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements., Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides., Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS., (Copyright © 2011. Published by Elsevier B.V.)

We describe a case of disseminated Penicillium marneffei in a human immunodeficiency virus (HIV)-positive Italian man who stayed for 4 years in Chiang Ray province, northern Thailand. A review of the literature shows that penicilliosis, although unusual, may represent an emerging opportunistic infection among HIV-positive people traveling to endemic areas.

We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area.

Objective: To describe the immunological and virological outcome, and the factors associated to discontinuation in patients switching to a regimen containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC) after long-term viral suppression under protease inhibitor-including HAART., Design: Observational study at three outpatient clinics for HIV care in Italy., Methods: Patients with HIV RNA <80 copies/ml and CD4 >200 cells/ml for at least 6 months on a protease inhibitor-containing treatment who switched to NVP, EFV or ABC were included in the study. End-points were immunological failure, virological failure and discontinuation due to toxicity. Survival analyses were performed to find out any independent variables predictive of reaching the end-points., Results: 177 patients were enrolled; 85 started EFV, 54 NVP and 38 ABC as part of the simplification regimen. 16/159 patients experienced immunological failure: the variables associated to CD4 count decrease were HIV RNA set point value (HR 2.32 for each log10 copies more, P=0.040) and intolerance/toxicity as reason for simplification (HR 3.96, P=0.05). 13/151 subjects showed virological failure; an AIDS diagnosis (HR 6.04, P=0.021) and the use of NVP (HR 7.98, P=0.027) were associated to a worse virological outcome, while patients naive before HAART showed a lower risk of failure (HR 0.008, P=0.007). 16/177 patients discontinued simplification regimen due to toxicity; longer HAART duration before switch was associated to risk reduction (HR 0.92, P=0.004)., Conclusions: Simplification is safe and effective, but it should be offered to patients with shorter treatment duration, and in good clinical and immunovirological conditions.

The immunovirological outcome of lopinavir/ritonavir was evaluated in 70 antiretroviral-experienced HIV patients; at baseline, median CD4+ cell count was 218 cells/mm(3) and median plasma viraemia 4.58 log(10) copies/mL. After 12 months, we observed an increase in CD4+ cell count to 322 cells/mm(3) (P = 0.0001) and a decrease in plasma viraemia to 2.35 log(10) copies/mL (P = 0.0001). Four patients discontinued lopinavir/ritonavir during observation. Among metabolic parameters, only triglyceride concentrations increased during treatment (P = 0.02). Twenty-six patients had a genotypic resistance test at baseline; four had > or =6 mutations known to reduce susceptibility to lopinavir/ritonavir. Undetectable plasma viraemia was obtained only in patients with < or =5 mutations (61.9%).