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Abstract Daptomycin is licensed in adults for the management of Staphylococcus aureus methicillin-resistant infections, including bone and skin complicated infections. We describe for the first time its use in a renal transplant recipient for Fabry-Anderson Disease with right heel osteomyelitis. The patient was unresponsive to first-line Teicoplanin and second-line Tigecycline, whereas he was successfully treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local debridement was performed in advance of each line of treatment.

Abstract Background Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors. Methods Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method. Results Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression). Conclusions Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden.

Abstract Introduction Selection of the K103N mutation is associated with moderately reduced in vitro fitness of HIV. Strains bearing K103N in vivo tend to persist, even in the absence of additional drug pressure, as minority quasispecies, often undetectable in genotyping resistance testing assays, performed at standard conditions. Here, we report on the rapid and long lasting selection of a K103N bearing strain as the dominant quasispecies after very short exposure to efavirenz in vivo. Case presentation A 55-year-old Caucasian man was switched to efavirenz, zidovudine and lamivudine in February 2003, while on viral suppression in his first-line highly active anti-retroviral treatment regimen. One month later, he reported inconsistent adherence and his viremia level was 5700 c/mL. He did not attend further checkups until September 2005, when his viral load was 181,000 c/mL. The patient reported interrupting his medications approximately three weeks after simplification. The genotyping resistance testing assay was performed both on HIV RNA and HIV DNA from plasma, yielding an identical pattern with the isolate presence of the K103N mutation in the prevalent strain. Conclusion Persistence of the K103N mutation as a majority quasispecies may ensue after a very short exposure to efavirenz. Our case would therefore suggest that the presence of the K103N mutation should always be ruled out by genotyping resistance testing assays, even after minimal exposures to efavirenz.

We carried out a prospective observational study to evaluate whether Monocyte Distribution Width (MDW) may play a role in identifying patients with sepsis in comparison with Procalcitonin (PCT). We prospectively enrolled all consecutive patients hospitalized at the Infectious Diseases Unit of Pescara General Hospital for bacterial infection or sepsis. MDW values were collected for all patients. Clinical characteristics, demographic data, past and present medical history, microbiological results, PCT, as well as neutrophil and monocytes indices at entry were compared in the 2 groups. Two-hundred-sixty patients were enrolled, 63.5% males, aged 59.1±19.5 years. Sepsis was diagnosed in 105 (40.4%); in 60 (57.1%) at least 1 microorganism was isolated from blood cultures. In multivariate models, MDW as a continuous variable (OR:1.57 for each unit increase; 95%CI: 1.31–1.87, p<0.001) and PCT˃1 ng/mL (OR: 48.5; 95%CI: 14.7–160.1, p<0.001) were independently associated with sepsis. Statistical best cut points associated with sepsis were 22.0 for MDW and 1.0 ng/mL for PCT whereas MDW values<20 were invariably associated with negative blood cultures. At ROC curve analysis, the AUC of MDW (0.87) was nearly overlapping that of PCT (0.88). Our data suggest that incorporating MDW within current routine WBC counts and indices may be of remarkable use for detection of sepsis. Further research is warranted. [ABSTRACT FROM AUTHOR]

Undiagnosed cases of HIV infection in developed countries are estimated at 20-30% of individuals living with HIV.Web-based strategies may represent a new approach to easier, wider, and unrestricted access to early testing. The Abruzzo Region, Italy, developed a Web-based tool to recruit persons at high risk of HIV and other sexually transmitted infections (STIs). At the Website www.failtestanchetu.it, browsers found information on STIs (HIV, hepatitis B and C, and syphilis), a structured questionnaire called "risk calculator" to assess one's own risk behaviors and direct booking of their test at one of six sites throughout the region. The Website was advertised on local media and in pharmacies, high schools, sports facilities, and factories. Between February 1, 2014, and May 31, 2015, about 6000 users visited the Website; 3046 people attended a visit for counseling on risk behaviors, signs, or symptoms of STIs and accepted blood drawing for HIV, hepatitis B Virus (HBV), hepatitis C Virus (HCV), and syphilis tests. Fifty-eight (1.90%) subjects were positive for HCV, 56 (1.84%) for HBsAg, 90 (2.95%) for Treponema pallidum antibodies, and 28 (0.92%) for HIV. Ninety-two percent of HIV-positive patients were successfully linked to care. Late presenters were less frequent in this sample than in the population diagnosed with HIV in Italy in 2014. An overall 7% proportion of HIV, HBV, HCV, and syphilis-unaware cases were all transferred to care, with the exception of three people. HIV seropositivity among testers was higher than 2/1000, the cost-effectiveness threshold suggested for effective testing. Therefore, our Web-based unrestricted and free access methodology appears worth further and wider evaluation. [ABSTRACT FROM AUTHOR]

Residual HIV viremia, defined by low levels of plasma HIV RNA with enhanced-sensitivity assays, may persist even in the presence of successful antiretroviral therapy, but little is known about its determinants. Our objective was to evaluate the rate and determinants of residual viremia in patients who show stable undetectable plasma HIV-1 RNA with conventional assays. Forty-four multidrug-experienced patients with undetectable levels of HIV RNA for at least 2 years under raltegravir-based regimens were evaluated. An ultrasensitive (2.5 copies/ml) real-time PCR method was used to quantify plasma HIV RNA. After 12 months of salvage treatment, 48.3% of the patients had residual viremia between 2.5 and 37 copies/ml. The proportion of patients with plasma HIV RNA below 2.5 copies/ml decreased from 51.7% at 12 months to 30.8% at 24 months. The presence of residual viremia was not associated with levels of viremia before starting raltegravir. Considering CD4 counts, hepatitis B or C virus (HBV or HCV) coinfection, or other demographic characteristics, for the time interval between HIV diagnosis and initiation of antiretroviral therapy, patients with a longer interval (>1 year) were significant less likely to have RNA levels below 2.5 copies/ml at 12 months compared to patients who started therapy within 1 year of HIV diagnosis (28.6% vs. 73.3%, p=0.027). Half of the patients showing undetectable HIV viremia with conventional assays had low-level viremia with ultrasensitive assays, with no predictive role of viroimmunological status at the start of the regimen. The potential influence of the interval between HIV diagnosis and initiation of treatment should be confirmed in subjects with a known date of seroconversion. [ABSTRACT FROM AUTHOR]

Background: Psychological factors are known predictors of cardiovascular disease in many clinical settings, but data are lacking for HIV infection. We carried out a prospective cohort study to evaluate potential psychological predictors of preclinical and clinical vascular disease in HIV patients. Methodology/Principal Findings: HIV patients were consecutively enrolled. Demographics, viral and immune parameters and traditional cardiovascular predictors were considered; Intima-Media Thickness (c-IMT, continuous measure) and Carotid Plaques (CPs, focal thickening ≥1.5 mm) were investigated by B-mode ultrasonography; depressive symptoms by the Beck Depression Inventory (BDI-II), Type D personality (Distressed Personality or Type D) by the DS14, alexithymia by the Toronto Alexithymia Scale (TAS-20). Vascular outcomes included transient ischemic attacks or stroke, acute coronary syndrome, myocardial or other organ infarction. We enrolled 232 HIV subjects, 73.9% males, aged 44.5±9.9 y, 38.2% with AIDS diagnosis, 18.3% untreated. Mean Nadir CD4 T-cell counts were 237.5±186.2/mmc. Of them, 224 (96.5%) attended IMT measurements; 201 (86.6%) attended both IMT assessment and psychological profiling. Mean follow-up was 782±308 days. Fifty-nine patients (29.4%) had CPs at baseline. Nineteen patients (9.5%) had ≥1 vascular event; 12 (6.0%) died due to such events (n = 4) or any cause. At baseline cross-sectional multivariate analysis, increasing age, total cholesterol, current smoking and Alexithymia score≥50 were significantly associated with both increased cIMT (linear regression) and CPs (logistic regression). At follow-up analysis, log-rank tests and Cox's regression revealed that only older age (p = 0.001), current smoking (p = 0.019) and alexithymia score≥50 (p = 0.013) were independently associated with vascular events. Conclusions/Significance: In HIV-infected subjects, the Alexithymic trait emerges as a strong predictor of increased IMT, presence of CPs and vascular events. Such results are preliminary and require confirmation from studies with larger sample size and longer follow-up. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors. Methods: Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs) at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC) method. Results: Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years); 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression). PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model). The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression). Conclusions: Smoking, traumas and surgery at the HZ site emerged as new predictors of both HZ-related pain intensity and persistence, opening new perspectives in the prevention of HZ-related pain. An independent line of evidence was provided for the efficacy of antiviral therapy in preventing PHN and reducing total pain burden. [ABSTRACT FROM AUTHOR]

Background Psychological factors (PFs) are known predictors of cardiovascular disease (CVD) in many clinical settings, but data are lacking for human immunodeficiency virus (HIV) infection. We carried out a prospective study to evaluate (1) psychological predictors of preclinical and clinical vascular disease and (2) all-cause mortality (ACM) in HIV patients. Methods We conducted a cross-sectional analysis of baseline data to evaluate the predictors of carotid plaques (CPs) and a prospective analysis to explore predictors of vascular events (VEs) and ACM over 10 years. Human immunodeficiency virus patients monitored at the Infectious Disease Units of 6 Italian regions were consecutively enrolled. Traditional CVD risk factors, PFs (depressive symptoms, alexithymia, distress personality), and CPs were investigated. Vascular events and ACM after enrollment were censored at March 2018. Results A multicenter cohort of 712 HIV-positive patients (75.3% males, aged 46.1 ± 10.1 years) was recruited. One hundred seventy-five (31.6%) patients had CPs at baseline. At the cross-sectional analysis, alexithymia was independently associated with CPs (odds ratio, 4.93; 95% confidence interval [CI], 2.90–8.50; P <.001), after adjustment for sociodemographic, clinical, and psychological variables. After an average follow-up of 4.4 ± 2.4 years, 54 (7.6%) patients developed a VE, whereas 41 (5.68%) died. Age, current smoking, hypertension, and alexithymia (hazard ratio [HR], 3.66; 95% CI, 1.80–7.44; P <.001) were independent predictors of VE. Likewise, alexithymia was an independent predictor of ACM (HR, 3.93; 95% CI, 1.65–9.0; P =.002), regardless of other clinical predictors. Conclusions The present results validate our previous monocentric finding. Alexithymia may be an additional tool for the multifactorial assessment of cardiovascular risk in HIV. [ABSTRACT FROM AUTHOR]

Background: HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015., Methods: Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai ® ) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter ® ) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test)., Results: 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described., Conclusions: More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease., Competing Interests: Conflict of interest The authors certify that there is no conflict of interest regarding the material discussed in the manuscript.

Introduction: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients., Methods: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed., Results: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002)., Discussion: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs., (Copyright © 2021 by The American College of Gastroenterology.)

Background: As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression., Methods: With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables., Results: We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782-29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001)., Conclusion: Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted.

Epstein-Barr virus (EBV) has been associated with primary central nervous system lymphoma and other EBV-related malignancies in HIV infected patients, and detection of EBV DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) has been demonstrated to be a good marker of PCNSL. Conversely, EBV has been rarely associated with encephalitis in HIV patients. Here we describe for the first time the case of an HIV-infected, late presenter Caucasian man, diagnosed with a rapidly progressive diffuse encephalitis at presentation. A very high viral load for EBV was detected in CSF by PCR. The patient died 12 days after the onset of encephalitis in spite of supportive, antiviral and antiretroviral therapy. Our experience would suggest that in profoundly immunosuppressed HIV patients EBV may cause severe encephalitis in the absence of lymphoproliferative disorders.

Coinfection by the Human Immunodeficiency Virus (HIV) and hepatitis viruses is a frequent condition in drug addicts. In the present study we report on the case of a patient with a history of drug and alcohol abuse who was sequentially infected with HIV, HCV, HBV and HDV. He died of an overwhelming reactivation of HBV and HDV in spite of a recent interferon treatment. HBV and HDV resumed their active replication after over 20 years of complete latency, that is after long-lasting viral undetectability, when the patient deliberately discontinued his last HAART regimen. HBV and HDV reactivated in spite of a relatively preserved immune system and a recent immune stimulatory treatment with pegylated interferon.

Transmission of drug-resistant HIV-1 variants has been increasingly documented. The most commonly observed resistance-associated mutations are thymidine analogue mutations as well as non-nucleoside reverse transcriptase inhibitor mutations. We report on a case of secondary transmission of a protease inhibitor (PI) primary mutation from an infected untreated subject to his sexual partner. Sequences isolated from the 2 patients showed a high level of identity (>99%), both carrying the major IAS PI mutation M46I. The latter mutation persisted in the bloodstream of the female partner 1 year after its first detection.

This case report is a case history of a femoral prosthesis infection caused by Rhodotorula mucilaginosa in a human immunodeficiency virus patient. Though the pathogenicity of this organism for bone tissue has been previously reported, this is the first reported case of an orthopedic prosthesis infection by this species of the genus Rhodotorula.