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Oral HPV infection is the main risk factor for the development of oropharyngeal carcinoma. Men who have sex with men (MSM), especially if living with HIV (PLWH), are at increased risk of infection and consequently of cancer development. Aim of this study is to evaluate the impact of nonavalent vaccine on oral HPV infection in a cohort of MSM and transgender women (TGW). This prospective study included all MSM and TGW who started nonavalent HPV vaccination from May 2019 to September 2021. Oral rinse was collected before each vaccine administration and after six months of follow up. Descriptive statistics were used. Kaplan Meier probability curves and Cox regression models for HPV acquisition and clearance were calculated. The analysis included 211 individuals (202 MSM and 9 TGW). PLWH were 138 (65.4%). Baseline oral rinse was positive in 30 subjects (14.2%). Positivity rate did not change over time (p = 0.742), even when restricting the analysis only to high-risk genotypes (p = 0.575) and to genotypes covered by vaccine (p = 0.894). The risk to acquire HPV infection was 12.8% at one year and 33.4% at two years after vaccination. The probability to clear the infection was 67.6% at one year and 87.9% at two years. HIV infection had no impact on vaccine efficacy. Age above 45 years was the only factor associated to HPV acquisition (aHR 4.06, 95% CI 1.03-15.98, p = 0.045). Prevalence of oral HPV infection was higher in PLWH, but HIV had no impact on viral clearance or acquisition after vaccination.
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Homossexualidade Masculina , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Pessoas Transgênero , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Pessoas Transgênero/estatística & dados numéricos , Adulto , Homossexualidade Masculina/estatística & dados numéricos , Feminino , Vacinas contra Papillomavirus/administração & dosagem , Pessoa de Meia-Idade , Vacinação/estatística & dados numéricos , Adulto Jovem , Papillomaviridae/genética , Papillomaviridae/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Fatores de Risco , Boca/virologiaRESUMO
OBJECTIVES: The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real-world setting. DESIGN: Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV-monoinfected; (b) HIV-positive/HBcAb-positive/HBsAg-negative; (c) HIV-positive/HBsAg-positive. The occurrence of VR, defined as two consecutive HIV-RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. METHODS: Standard survival analysis by means of Kaplan-Meier curves and Cox regression analysis with the serology exposure fitted as a time-fixed covariate measured at baseline was employed after controlling for key confounding factors. RESULTS: Of a total of 5657 patients included, 4090 (72%) were HIV-monoinfected, 1342 (23.7%)were HBcAb-positive, and 225 (3.9%) were HbsAg-positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow-up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV-monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg-positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03-2.38, p = 0.037] but an excess of risk was also seen in those who were HIV-positive/HBcAb-positive/HBsAg-negative (aHR = 1.25, 95% CI: 1.00-1.55, p = 0.047). CONCLUSIONS: Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV-monoinfected and their HIV-RNA should be carefully monitored.
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The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.
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Antivirais , Carcinoma Hepatocelular , Hepacivirus , Hepatite C Crônica , Neoplasias Hepáticas , Pontuação de Propensão , Resposta Viral Sustentada , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Masculino , Antivirais/uso terapêutico , Feminino , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Pessoa de Meia-Idade , Idoso , Incidência , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Cirrose Hepática/virologia , Cirrose Hepática/epidemiologia , Estudos Prospectivos , Itália/epidemiologia , Fatores de Risco , Estudos de Coortes , AdultoRESUMO
Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.
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Meningitis and ventriculitis, due to carbapenem-resistant Enterobacterales, are frequently associated with significant morbidity and mortality. In the case of multi-drug-resistant pathogens, it is necessary to consider the limited susceptibility profile as well as the penetration of the antimicrobials into the brain. Limited data are available regarding the treatment of central nervous system infections caused by carbapenem-resistant Enterobacterales. We report a study of a patient treated with meropenem-vaborbactam in the case of post-neurosurgical meningitis due to carbapenemase-producing Klebsiella pneumoniae (CPKP).
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Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug-drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs' risk stratification), and new antifungals and their features (rezafungin and olorofim).
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OBJECTIVES: The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)-based two-drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not-detected maintenance over time. METHODS: This retrospective, monocentric analysis included all subjects who started a DTG-based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non-parametric tests to describe and compare the groups were applied. Kaplan-Meier probability curves and Cox regression models for regimens durability were used. RESULTS: The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance-associated mutations, and a worse immune-virologic status. Over a cumulative follow-up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow-up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. CONCLUSIONS: DTG + DOR durability was high over a long follow-up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat.
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Fármacos Anti-HIV , Quimioterapia Combinada , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piperazinas , Piridonas , Triazóis , Humanos , Estudos Retrospectivos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Pessoa de Meia-Idade , Triazóis/uso terapêutico , Triazóis/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Rilpivirina/uso terapêutico , Rilpivirina/administração & dosagem , Carga Viral/efeitos dos fármacosRESUMO
OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.
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Carcinoma Hepatocelular , Coinfecção , Usuários de Drogas , Infecções por HIV , Hepatite C , Hepatite D , Neoplasias Hepáticas , Abuso de Substâncias por Via Intravenosa , Masculino , Humanos , Feminino , Vírus Delta da Hepatite/genética , Antígenos de Superfície da Hepatite B , Carcinoma Hepatocelular/epidemiologia , Coinfecção/epidemiologia , Neoplasias Hepáticas/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Hepatite D/complicações , Hepatite D/epidemiologia , Anticorpos Anti-Hepatite , Prevalência , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , RNA , Hepatite C/complicações , Vírus da Hepatite B/genéticaRESUMO
Mycoplasma genitalium (MG) is a common cause of non-gonococcal urethritis, but a role in acute or chronic prostatitis has not been described. We describe the case of a 42-year-old man with recurrent urinary tract infections since 2018 who developed chronic prostatitis despite several and prolonged antibiotic courses. Multiparametric prostatic magnetic resonance showed peripheral inflammatory alterations. A 4-glass Meares-Stamey test detected MG in the third voided bladder (VB3) sample. Moxifloxacin 400 mg daily for 28 days resulted in sustained clinical and microbiological cure.
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Infecções por Mycoplasma , Mycoplasma genitalium , Prostatite , Uretrite , Masculino , Humanos , Adulto , Prostatite/diagnóstico , Prostatite/tratamento farmacológico , Antibacterianos/uso terapêutico , Uretrite/diagnóstico , Uretrite/tratamento farmacológico , Uretrite/microbiologia , Doença Crônica , Infecções por Mycoplasma/complicações , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/tratamento farmacológicoRESUMO
INTRODUCTION: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. METHODS: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. RESULTS: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. CONCLUSIONS: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.
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BACKGROUND AND AIM: The World Health Organization (WHO) goal of Hepatitis C Virus (HCV) elimination by 2030 rose awareness about the need of screening plans, worldwide. In Italy, graduated screening starting from people born in 1969-1989 might be the most-effective strategy. We performed an opportunistic HCV screening study in the general population attending health facilities in Lombardy region, Northern Italy. METHODS: This is a prospective, multicenter, territory-wide, opportunistic study supported by the Regional Government of Lombardy, Italy. Between June 2022 and December 2022, all subjects born in 1969-1989, hospitalized or accessing blood collection centres were offered anti-HCV and HCV-RNA tests. Patients with known anti-HCV positivity and/or previous anti-HCV treatment were excluded. Demographic features were uploaded into a regional web-based platform. RESULTS: In total, 120 193 individuals were screened in 75 centres. Mean age was 44 (±6) years, 65.2% were females, 83.7% were tested at blood collection centres. Anti-HCV tested positive in 604 (0.50%) subjects: mean age 47 (±5), 51.1% females. HCV seroprevalence was higher in males (p < 0.00001), elderly (p < 0.00001) and in- vs. outpatients (p = 0.0009). HCV-RNA was detectable in 125 out of 441 (28.3%) anti-HCV positive subjects. Actively infected patients were 46 (±6) years old, mainly males (56.8%). The overall prevalence of active HCV infection was 0.10%, higher in elderly (p = 0.0003) and in in-patients (p = 0.0007). Among 93 HCV-RNA positive patients, the median age was 48 years, 58% males, 62% Italian born, median HCV-RNA levels were 6,1 log IU/mL, liver stiffness measurement (LSM) values 5.5 (3.1-29.9) kPa and ALT levels 48 U/L. CONCLUSIONS: The prevalence of active HCV infection in the 1969-1989 population attending health facilities in Lombardy was low. Most viremic patients were Italian-born, with mild liver disease but high-HCV-RNA levels. Due to the higher prevalence in the elderly, the extension of such opportunistic screening programs to lower birth cohorts would be warranted.
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Hepacivirus , Hepatite C , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Adulto , Hepacivirus/genética , Estudos Soroepidemiológicos , Coorte de Nascimento , Estudos Prospectivos , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Programas de Rastreamento , Prevalência , Hospitais , RNA Viral , Itália/epidemiologia , Anticorpos Anti-Hepatite CRESUMO
BACKGROUND: B-cell-depleting treatments, such as ocrelizumab and rituximab (anti-CD20), reduce humoral response to SARS-CoV-2 in people with Multiple Sclerosis (pwMS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) and are associated with an increased risk of a more severe course of COVID-19 disease. The combination of tixagevimab and cilgavimab was authorized for COVID-19 prevention in immunocompromised subjects at high risk of severe COVID-19 disease, including patients treated with anti-CD20. Few real-world studies are available regarding the use of tixagevimab/cilgavimab in pwMS/NMOSD. In the present study, we describe the use of tixagevimab/cilgavimab for SARS-CoV-2 pre-exposure prophylaxis in a cohort of pwMS and NMOSD, treated with ocrelizumab and rituximab respectively. METHODS: 26 subjects were treated with tixagevimab/cilgavimab, while we used 18 patients as the control group. We collected clinical data at baseline in all patients and during scheduled follow up evaluations. SARS-CoV-2 serological status pre- and post-tixagevimab/cilgavimab treatment was available for 10 patients. RESULTS: We observed no adverse events following tixagevimab/cilgavimab treatment. Post-tixagevimab/cilgavimab anti-Spike-1-RBD IgG were significantly higher when compared to baseline values. No difference was found when comparing the percentage of COVID-19 infections between groups. All patients infected with SARS-CoV-2 had mild disease which did not require hospitalization. In patients treated with tixagevimab/cilgavimab, the rate of infection among patients exposed to SARS-CoV-2 was lower, without reaching statistical significance. We observed a significantly longer negativization time in the treated group. CONCLUSIONS: Our results are not consistent with what was observed in the registration trial and some more recent studies. We did not observe a difference in COVID-19 incidence nor in disease severity in MS and NMOSD between treated and untreated patients. Our different results may be partially explained by the change in SARS-CoV-2 variants epidemiology (i.e. reduced efficacy of tixagevimab and cilgavimab against the currently dominant variants) as well as different patient selection included in the trial and different dose of tixagevimab/cilgavimab used in other studies. The present report provides a real-life experience with tixagevimab/cilgavimab in pwMS and NMOSD treated with anti-CD20, with findings that are in line with the current SARS-CoV-2 epidemiology and the recent evidence regarding SARS-CoV-2 variants. Our results warrant further research to best treat patients in the present and future pandemic scenario.
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COVID-19 , Esclerose Múltipla , Neuromielite Óptica , Humanos , SARS-CoV-2 , Rituximab/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Neuromielite Óptica/tratamento farmacológicoRESUMO
Detection of subgenomic (sg) SARS-CoV-2 RNAs are frequently used as a correlate of viral infectiousness, but few data about correlation between sg load and viable virus are available. Here, we defined concordance between culture isolation and E and N sgRNA quantification by ddPCR assays in 51 nasopharyngeal swabs collected from SARS-CoV-2 positive hospitalized patients. Among the 51 samples, 14 were SARS-CoV-2 culture-positive and 37 were negative. According to culture results, the sensitivity and specificity of E and N sgRNA assays were 100% and 100%, and 84% and 86%, respectively. ROC analysis showed that the best E and N cut-offs to predict positive culture isolation were 32 and 161 copies/mL respectively, with an AUC (95% CI) of 0.96 (0.91-1.00) and 0.96 (0.92-1.00), and a diagnostic accuracy of 88% and 92%, respectively. Even if no significant correlations were observed between sgRNA amount and clinical presentation, a higher number of moderate/severe cases and lower number of days from symptoms onset characterized patients with sgRNA equal to or higher than sgRNA cut-offs. Overall, this study suggests that SARS-CoV-2 sgRNA quantification could be helpful to estimate the replicative activity of SARS-CoV-2 and can represent a valid surrogate marker to efficiently recognize patients with active infection. The inclusion of this assay in available SARS-CoV-2 diagnostics procedure might help in optimizing fragile patients monitoring and management.
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COVID-19 , Viroses , Humanos , COVID-19/diagnóstico , SARS-CoV-2/genética , RNA Subgenômico , Biomarcadores , RNARESUMO
Purpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS). Patients and Methods: During 01/2011-06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated. Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases. Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.
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BACKGROUND AND AIMS: Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. METHODS: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. RESULTS: Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36-.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91-2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17-2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62-.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56-.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07-.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. CONCLUSIONS: The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort.
Assuntos
COVID-19 , Infecções por HIV , Hepatite C , Humanos , Criança , Antivirais/uso terapêutico , Estudos Prospectivos , Reinfecção , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , RNA , Viremia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologiaRESUMO
HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co-infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co-infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co-infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti-thyroglobulin Ab, anti-thyroid peroxidase Ab, ANCA, ASMA, anti-LKM, anti-DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0-F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti-thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p < .001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p = .099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks.
Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Humanos , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fator Reumatoide , Estudos Prospectivos , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Autoanticorpos/uso terapêutico , Hepacivirus/genética , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. METHODS: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. RESULTS: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% at 12-, 24- and 36-months from end-of-therapy, respectively (incidence rate 2.45/100 person-years). Age, genotype 3, diabetes, platelets (PLT)≤120,000/µl and albumin ≤3.5g/dl levels were identified as pre-treatment HCC independent predictors. Adjusting for age, the post-treatment PLT≤120,000/µl (AdjHR 1.92; 95%CI:1.06-3.45) and albumin≤3.5g/dl (AdjHR 4.38; 95%CI 2.48-7.75) values were independently associated with HCC occurrence. Two different risk profiles were identified by combining long-term post-therapy evaluation of PLT ≤ vs. >120,000/µl and albumin ≤ vs. >3.5g/dl showing a significant different HCC incidence rate of 1.35 vs. 3.77/100 p-y, respectively. CONCLUSIONS: The nomogram score based on age, PLT and albumin levels after SVR showed an accurate prediction capability and may support the customizing management for early HCC detection.