Loredana Sarmati - Academia.edu (original) (raw)

Papers by Loredana Sarmati

Research paper thumbnail of HBV-HDV co-infection constrains HBV genetic evolution in HBsAg

Digestive and Liver Disease, 2016

In this cross-sectional analysis we aimed to characterize the HIV-HCV co-infected patients enroll... more In this cross-sectional analysis we aimed to characterize the HIV-HCV co-infected patients enrolled in the PITER cohort. The cohort includes, as of the time of this analysis, 7359 consecutively enrolled patients from 80 Italian clinical centers. HIV infection was present in 448 (6.5%) of patients with HCV chronic infection consecutively enrolled in PITER. HIV-HCV co-infected vs HCV mono-infected patients presented the following characteristics: a significantly different distribution of HCV genotypes (Gt1a:28% vs 11%, Gt 1b:17% vs 44%, Gt 2:3% vs 15%, Gt 3:24% vs 10%, Gt 4:14% vs 6% respectively); a similar fibrosis stage (F1-F3), with F4/cirrhosis in 41% vs 47%, despite the significant younger age (51 ± 6 vs 61 ± 12 years respectively) (p < 0.01) and significant differences in the prevalence of the following comorbidities: cardiovascular 20% vs 29%; psychiatric 13% vs 8%; osteoarticular 11% vs 5% neurologic in 8% vs 3% and diabetes in 8% vs 13% patients respectively. Regarding anti-HIV treatment, the following regimens were used: 54% of patients were on PIs, 42% on INSTIs and 4% on CCR5s. Regarding previous anti-HCV therapy, 33% of HIV-HCV co-infected compared to 53% of HCV mono-infected patients were experienced to IFN based treatment. HCV treatment is considered as a priority for HIV co-infected individuals, however the prioritization algorithm endorsed by AIFA, could allow reimbursement of DAAs in Italy only for about 41% of HIV-HCV co-infected patients with F4/cirrhosis. Conclusions: Allocation of DAA, according to the priority rules, should consider access to therapy in all HIV-HCV coinfected patients, independently of fibrosis stage. Differences in sociodemografic, virological, and comorbidities pattern in HIV-HCV co-infected patients vs. mono-infected patients should be considered to better define the DAA's treatment strategies in them. Data from PITER cohort will hopefully contribute to the revision of HCV treatment priorities in Italy.

Research paper thumbnail of Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications

BMC Public Health, May 28, 2019

Background: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV)... more Background: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). Methods: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. Results: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm 3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. Conclusions: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Research paper thumbnail of Bictegravir/emtricitabine/tenofovir alafenamide ensures high rates of virological suppression maintenance despite previous resistance in PLWH who optimize treatment in clinical practice

Journal of global antimicrobial resistance, Sep 1, 2022

Research paper thumbnail of New insights into hepatitis B virus lymphotropism: Implications for HBV-related lymphomagenesis

Frontiers in Oncology

HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic ... more HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and in vitro studies has been reported. In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin’s lymphoma (NHL) (HR 2.10 [95% CI 1.34-3.31], p=0.001) and, more specifically, all NHL B subtypes (HR 2.14 [95% CI 1.61-2.07], p<0.001). Questionable and unconfirmed associations are reported between HBV and NHL T subtypes (HR 1.11 [95% CI 0.88-1.40], p=0.40) and leukemia. The presence of HBV DNA in peripheral blood mononuclear cells has been ...

Research paper thumbnail of Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

Viruses

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies... more The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35–14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly ...

Research paper thumbnail of 1438. Latent tuberculosis infection (LTBI) in hematopoietic stem cell transplantation (HSCT) recipients: a retrospective Italian cohort study in Tor Vergata University Hospital, Rome

Open Forum Infectious Diseases

Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and pr... more Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and prolonged immunodeficiency and the incidence of tuberculosis (TB) disease in those patients is 10 to 40 times higher than the general population Methods This retrospective study performed at Tor Vergata University Hospital in Rome (Italy) included all adult patients who underwent a HSCT in the Hematologic Transplant Unit from January 2015 to December 2019. Data on TB screening, performed through interferon-γ release assay (IGRA), were collected; patients were observed for TB reactivation in a follow up period of at least 3 years Results 323 HSCT recipients were enrolled in this study. Patients’ characteristics are summarized in table 1. 63 patients (19.5%) were not screened for TB, of which 6.3% were born overseas. 260 HSCT recipients (80.5%) were screened: 228 patients (87.7%) had a negative IGRA result, 21 (8.1%) tested positive, and 11 (4.2%) had an indeterminate result. 98.5% were scre...

Research paper thumbnail of Hepatitis B-related hepatic flare during immune reconstitution syndrome after antiretroviral treatment initiation in an HBV surface antigen-positive patient with HIV: viroimmunological and histological characterization

Open Forum Infectious Diseases

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is relatively common. ... more Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA (ihHBV-DNA), covalently closed circular DNA (cccDNA), and HBV pregenomic RNA (pgRNA) through a droplet digital (dd)PCR system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART ini...

Research paper thumbnail of In Patients with Severe COVID-19, the Profound Decrease in the Peripheral Blood T-Cell Subsets Is Correlated with an Increase of QuantiFERON-TB Gold Plus Indeterminate Rates and Reflecting a Reduced Interferon-Gamma Production

Life, 2022

Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in p... more Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in patients hospitalized with Coronavirus Disease (COVID)-19. We aimed to define the prevalence and characteristics of hospitalized COVID-19 patients with indeterminate QFT-Plus. A retrospective study was performed including hospitalized COVID-19 patients, stratified in survivors and non-survivors, non-severe and severe according to the maximal oxygen supply required. Statistical analysis was performed using JASP ver0.14.1 and GraphPad Prism ver8.2.1. A total of 420 patients were included, median age: 65 years, males: 66.4%. The QFT-Plus was indeterminate in 22.1% of patients. Increased rate of indeterminate QFT-Plus was found in non-survivors (p = 0.013) and in severe COVID-19 patients (p < 0.001). Considering the Mitogen-Nil condition of the QFT-Plus, an impaired production of interferon-gamma (IFN-γ) was found in non-survivors (p < 0.001) and in severe COVID-19 patients (p < 0.00...

Research paper thumbnail of Parietal Intrahemispheric Source Connectivity of Resting-State Electroencephalographic Alpha Rhythms is Abnormal in Naïve Hiv Patients

Brain Research Bulletin, 2022

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG)... more Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4Hz) and alpha (8-12Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder. The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals. Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals. In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Research paper thumbnail of Key mutational patterns in HBsAg C-terminus profoundly affect HBsAg levels in HBeAg-negative chronic HBV genotype D infection

Journal of Hepatology, 2018

Research paper thumbnail of Biological phenotype, replicative capacity and drug resistance of HIV strains isolated from patients failing antiretroviral therapy

Research paper thumbnail of ISS-NIA Study Group. Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virusor hepatitis B virus coinfection

Research paper thumbnail of Limited occurence of new grade 3-4 toxicity events with salvage regimens based on raltegravir and /or maraviroc: 96 weeks data from the ISS NIA cohort study

Research paper thumbnail of Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation and out come after genotypic guided change of therapy

Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation an... more Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation and out come after genotypic guided change of therapy

Research paper thumbnail of Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

Journal of Translational Medicine, 2021

Following publication of the original article [1] the authors identified that the collaborators o... more Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article.

Research paper thumbnail of HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort

Microorganisms, 2021

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies... more The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0...

Research paper thumbnail of Tocilizumab for patients with COVID-19 pneumonia. The TOCIVID-19 prospective phase 2 trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in patho... more BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders.Resultsout of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, P<0.001) at 14 and 30 days. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be...

Research paper thumbnail of Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levels in vivo, hinder HBsAg secretion in vitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection

Emerging Microbes & Infections, 2020

HBsAg levels invivo, hinder HBsAg secretion invitro and reduce HBsAg structural stability in the ... more HBsAg levels invivo, hinder HBsAg secretion invitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection, Emerging Microbes & Infections,

Research paper thumbnail of The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro

Clinical Microbiology and Infection, 2018

Objective: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV)-r... more Objective: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. Methods: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pregenomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. Results: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). Conclusions: F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven

Research paper thumbnail of In HBeAg-negative chronic HBV infection, HBsAg levels profoundly differ among HBV-genotypes and can be affected by the extent of HBsAg variability: Can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

Digestive and Liver Disease, 2017

Research paper thumbnail of HBV-HDV co-infection constrains HBV genetic evolution in HBsAg

Digestive and Liver Disease, 2016

In this cross-sectional analysis we aimed to characterize the HIV-HCV co-infected patients enroll... more In this cross-sectional analysis we aimed to characterize the HIV-HCV co-infected patients enrolled in the PITER cohort. The cohort includes, as of the time of this analysis, 7359 consecutively enrolled patients from 80 Italian clinical centers. HIV infection was present in 448 (6.5%) of patients with HCV chronic infection consecutively enrolled in PITER. HIV-HCV co-infected vs HCV mono-infected patients presented the following characteristics: a significantly different distribution of HCV genotypes (Gt1a:28% vs 11%, Gt 1b:17% vs 44%, Gt 2:3% vs 15%, Gt 3:24% vs 10%, Gt 4:14% vs 6% respectively); a similar fibrosis stage (F1-F3), with F4/cirrhosis in 41% vs 47%, despite the significant younger age (51 ± 6 vs 61 ± 12 years respectively) (p < 0.01) and significant differences in the prevalence of the following comorbidities: cardiovascular 20% vs 29%; psychiatric 13% vs 8%; osteoarticular 11% vs 5% neurologic in 8% vs 3% and diabetes in 8% vs 13% patients respectively. Regarding anti-HIV treatment, the following regimens were used: 54% of patients were on PIs, 42% on INSTIs and 4% on CCR5s. Regarding previous anti-HCV therapy, 33% of HIV-HCV co-infected compared to 53% of HCV mono-infected patients were experienced to IFN based treatment. HCV treatment is considered as a priority for HIV co-infected individuals, however the prioritization algorithm endorsed by AIFA, could allow reimbursement of DAAs in Italy only for about 41% of HIV-HCV co-infected patients with F4/cirrhosis. Conclusions: Allocation of DAA, according to the priority rules, should consider access to therapy in all HIV-HCV coinfected patients, independently of fibrosis stage. Differences in sociodemografic, virological, and comorbidities pattern in HIV-HCV co-infected patients vs. mono-infected patients should be considered to better define the DAA's treatment strategies in them. Data from PITER cohort will hopefully contribute to the revision of HCV treatment priorities in Italy.

Research paper thumbnail of Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications

BMC Public Health, May 28, 2019

Background: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV)... more Background: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). Methods: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. Results: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm 3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. Conclusions: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Research paper thumbnail of Bictegravir/emtricitabine/tenofovir alafenamide ensures high rates of virological suppression maintenance despite previous resistance in PLWH who optimize treatment in clinical practice

Journal of global antimicrobial resistance, Sep 1, 2022

Research paper thumbnail of New insights into hepatitis B virus lymphotropism: Implications for HBV-related lymphomagenesis

Frontiers in Oncology

HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic ... more HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and in vitro studies has been reported. In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin’s lymphoma (NHL) (HR 2.10 [95% CI 1.34-3.31], p=0.001) and, more specifically, all NHL B subtypes (HR 2.14 [95% CI 1.61-2.07], p<0.001). Questionable and unconfirmed associations are reported between HBV and NHL T subtypes (HR 1.11 [95% CI 0.88-1.40], p=0.40) and leukemia. The presence of HBV DNA in peripheral blood mononuclear cells has been ...

Research paper thumbnail of Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort

Viruses

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies... more The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35–14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly ...

Research paper thumbnail of 1438. Latent tuberculosis infection (LTBI) in hematopoietic stem cell transplantation (HSCT) recipients: a retrospective Italian cohort study in Tor Vergata University Hospital, Rome

Open Forum Infectious Diseases

Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and pr... more Background Patients undergoing haematopoietic stem cell transplantation (HSCT) have severe and prolonged immunodeficiency and the incidence of tuberculosis (TB) disease in those patients is 10 to 40 times higher than the general population Methods This retrospective study performed at Tor Vergata University Hospital in Rome (Italy) included all adult patients who underwent a HSCT in the Hematologic Transplant Unit from January 2015 to December 2019. Data on TB screening, performed through interferon-γ release assay (IGRA), were collected; patients were observed for TB reactivation in a follow up period of at least 3 years Results 323 HSCT recipients were enrolled in this study. Patients’ characteristics are summarized in table 1. 63 patients (19.5%) were not screened for TB, of which 6.3% were born overseas. 260 HSCT recipients (80.5%) were screened: 228 patients (87.7%) had a negative IGRA result, 21 (8.1%) tested positive, and 11 (4.2%) had an indeterminate result. 98.5% were scre...

Research paper thumbnail of Hepatitis B-related hepatic flare during immune reconstitution syndrome after antiretroviral treatment initiation in an HBV surface antigen-positive patient with HIV: viroimmunological and histological characterization

Open Forum Infectious Diseases

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is relatively common. ... more Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA (ihHBV-DNA), covalently closed circular DNA (cccDNA), and HBV pregenomic RNA (pgRNA) through a droplet digital (dd)PCR system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART ini...

Research paper thumbnail of In Patients with Severe COVID-19, the Profound Decrease in the Peripheral Blood T-Cell Subsets Is Correlated with an Increase of QuantiFERON-TB Gold Plus Indeterminate Rates and Reflecting a Reduced Interferon-Gamma Production

Life, 2022

Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in p... more Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in patients hospitalized with Coronavirus Disease (COVID)-19. We aimed to define the prevalence and characteristics of hospitalized COVID-19 patients with indeterminate QFT-Plus. A retrospective study was performed including hospitalized COVID-19 patients, stratified in survivors and non-survivors, non-severe and severe according to the maximal oxygen supply required. Statistical analysis was performed using JASP ver0.14.1 and GraphPad Prism ver8.2.1. A total of 420 patients were included, median age: 65 years, males: 66.4%. The QFT-Plus was indeterminate in 22.1% of patients. Increased rate of indeterminate QFT-Plus was found in non-survivors (p = 0.013) and in severe COVID-19 patients (p < 0.001). Considering the Mitogen-Nil condition of the QFT-Plus, an impaired production of interferon-gamma (IFN-γ) was found in non-survivors (p < 0.001) and in severe COVID-19 patients (p < 0.00...

Research paper thumbnail of Parietal Intrahemispheric Source Connectivity of Resting-State Electroencephalographic Alpha Rhythms is Abnormal in Naïve Hiv Patients

Brain Research Bulletin, 2022

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG)... more Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4Hz) and alpha (8-12Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder. The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals. Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals. In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Research paper thumbnail of Key mutational patterns in HBsAg C-terminus profoundly affect HBsAg levels in HBeAg-negative chronic HBV genotype D infection

Journal of Hepatology, 2018

Research paper thumbnail of Biological phenotype, replicative capacity and drug resistance of HIV strains isolated from patients failing antiretroviral therapy

Research paper thumbnail of ISS-NIA Study Group. Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virusor hepatitis B virus coinfection

Research paper thumbnail of Limited occurence of new grade 3-4 toxicity events with salvage regimens based on raltegravir and /or maraviroc: 96 weeks data from the ISS NIA cohort study

Research paper thumbnail of Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation and out come after genotypic guided change of therapy

Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation an... more Patients with viro-immunologic discordant response to HAART: High prevalence of M184V mutation and out come after genotypic guided change of therapy

Research paper thumbnail of Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

Journal of Translational Medicine, 2021

Following publication of the original article [1] the authors identified that the collaborators o... more Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article.

Research paper thumbnail of HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort

Microorganisms, 2021

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies... more The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0...

Research paper thumbnail of Tocilizumab for patients with COVID-19 pneumonia. The TOCIVID-19 prospective phase 2 trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in patho... more BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders.Resultsout of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, P<0.001) at 14 and 30 days. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be...

Research paper thumbnail of Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levels in vivo, hinder HBsAg secretion in vitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection

Emerging Microbes & Infections, 2020

HBsAg levels invivo, hinder HBsAg secretion invitro and reduce HBsAg structural stability in the ... more HBsAg levels invivo, hinder HBsAg secretion invitro and reduce HBsAg structural stability in the setting of HBeAg-negative chronic HBV genotype-D infection, Emerging Microbes & Infections,

Research paper thumbnail of The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro

Clinical Microbiology and Infection, 2018

Objective: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV)-r... more Objective: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. Methods: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pregenomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. Results: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). Conclusions: F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven

Research paper thumbnail of In HBeAg-negative chronic HBV infection, HBsAg levels profoundly differ among HBV-genotypes and can be affected by the extent of HBsAg variability: Can quantitative HBsAg truly reflect intra-hepatic HBV reservoir?

Digestive and Liver Disease, 2017