Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Histoplasmosis in patients living with HIV in Europe: review of literature

histoplasma capsulatum (var. capsulatum Hcc and duboisii Hcd), is a dimorphic fungus that causes histoplasmosis. It usually affects people coming from endemic areas, causing a variety of clinical manifestations up to progressive disseminated histoplasmosis (PDH), especially among people living with HIV (PLWH). we conducted a systematic review to assess histoplasmosis burden of PLWH in europe. the review follows PRISMA guidelines, with protocol registered in PROSPERO (CRD42023429779). seventy-eight articles were selected, including 109 patients (32 women). on overall, median age was 37 years. forty-six patients were americans, 39 africans, 17 europeans, 5 asians, in 2 cases nationality was not specified. cases were mainly diagnosed in Italy (28.4%), france (17.3%) and spain (17.4%), with a north-south gradient. six cases lacked epidemiologic links with endemic areas. concerning CDC HIV staging at diagnosis, the information was available for 60 PLWH (55%) and all subjects were at stage C3 except for two subjects at stage B3. PDH was the AIDS-presenting illness in 39 patients. most patients had a PDH (80.7%); other common extrapulmonary forms were isolated cutaneous histoplasmosis (7.3%), or lymphatic localization (2.7%). In 30 cases, the diagnosis was made by analyzing only one sample. for the remaining 79 cases, multiple samples were collected from each patient. regarding the biological sample more frequently used for the diagnosis of histoplasmosis, bronchoalveolar lavage sample was taken from 39 patients, and tested positive in 51.3% of cases; 36 patients underwent a skin biopsy which was positive in 86.1% of cases and 28 patients performed bone-marrow biopsy, which led to the diagnosis of histoplasmosis in 92.9% of cases. the identification of histoplasma capsulatum was available in 97 PLWH through examination of different samples: Hcc and Hcd were identified in 89 and 8 PLWH, respectively. concerning therapies, 67.9% were treated with liposomal amphotericin B, 18.3% with itraconazole, 10 died pre-treatment. the overall mortality rate was 23.6%. non-survivors exhibited more frequently gastrointestinal symptoms (p = 0.017), while cutaneous signs correlated with better survival (p = 0.05). untreated patients faced higher mortality (p < 0.001). histoplasmosis should be considered amongst opportunistic infection in PLWH, even in europe, especially if patients originate from or have travelled to endemic areas

Incidence of pneumomediastinum in COVID-19: A single-center comparison between 1st and 2nd wave

In this study, we compared the incidence of pneumomediastinum in coronavirus disease (COVID-19) patients during the ascending phases of the 1st and 2nd epidemic waves. Crude incidence was higher during the 2nd wave at a quasi-significant level (0.68/1000 vs. 2.05/1000 patient-days, p = 0.05). When restricting the analysis to patients who developed pneumomediastinum during noninvasive ventilation, the difference became clearly significant (0.17/1000 vs 1.36/1000 patient-days, p = 0.039). At logistic regression, predisposing factors (p = 0.031), and COVID-19 radiological severity (p = 0.019) were independently associated with pneumomediastinum. Mortality in patients with pneumomediastinum was 87.5%. However, pneumomediastinum seemed to be related to a generally worse disease presentation in hospitalized patients during the 2nd wave, rather than to a separate pattern of disease. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved

Droplet digital PCR assay as an innovative and promising highly sensitive assay to unveil residual and cryptic HBV replication in peripheral compartment

: Droplet digital PCR is an innovative and promising approach for highly sensitive quantification of nucleic acids that is being increasingly used in the field of clinical virology, including the setting of hepatitis B virus (HBV). Here, we comprehensively report a robust and reproducible ddPCR assay for the highly sensitive quantification of serum HBV-DNA. The assay showed a limit of detection of 4 copies/ml (<1IU/ml) by Probit analysis, showed a good linearity (R2 = 0.94) and a high intra- and inter-run reproducibility with differences between the values obtained in the same run or in two independent runs never exceeding 0.14logcopies/mL and 0.21logcopies/mL, respectively. By analysing serum samples from chronically HBV infected patients (mostly under antiviral treatment), ddPCR successfully quantified serum HBV-DNA in 89.8% of patients with detectable serum HBV-DNA < 20 IU/mL [equivalent to <112copies/ml] by classical Real-Time PCR assay, with a median (IQR) of 8(5-14)IU/mL [45(28-78)copies/ml], and in 66.7% of patients with undetectable serum HBV-DNA, with a median (IQR) of 5(4-9)IU/mL [28(20-50)copies/ml]. Similarly, by analysing serum samples from patients with a serological profile compatible with occult HBV infection (anti-HBc+/HBsAg-), ddPCR successfully quantified serum HBV-DNA in 40% of patients with a median (IQR) value of 1(1-2)IU/mL [5(5-11)copies/ml], in line with the extremely limited viral replication typically observed in occult HBV infection. Overall, the availability of assays for the highly sensitive quantification of serum HBV-DNA can provide an added value in optimizing the diagnosis of occult hepatitis B infection, improving the therapeutic management of chronically HBV infected patients, also in the light of innovative drugs (upcoming in clinical practise) aimed at achieving HBV functional cure

Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study

The burden, microbial etiology and clinical impact of hospital-acquired respiratory infections (HARIs) were determined at an Italian teaching hospital over a 12-month period. For this purpose, overall ordinary hospitalizations >= 2 days of subjects over 18 years old with discharge from 1 January 2018 to 31 December 2018 were examined by cross-referencing demographic and clinical data from hospital discharge forms with microbiological data from the computer system of the Microbiology Unit. We identified 329 individuals with HARIs (96 females and 233 males; median age 70 years, range 18-93), who represented 1/4 of the total hospital-acquired infections (HAIs) in the period. The inpatient setting was medical and surgical in similar proportions (169 vs. 160, respectively) and the mean hospital stay was 38.9 +/- 33.6 days. One hundred and forty patients (42.6% of the total sample) were suffering from one or more chronic diseases. A total of 581 microorganisms (82 antibiotic-resistant and 499 non-resistant) were detected in HARI patients. The most common isolated species were Staphylococcus aureus (16.7%), Klebsiella pneumoniae (13.3%), Pseudomonas spp. (12.6%) and Acinetobacter baumannii (10.5%), followed by Enterobacter spp. (5.3%), Escherichia coli (5.2%) and Enterococcus spp. (4.8%). One hundred and sixty-seven individuals (49.0% of the total) had polymicrobial infections. One hundred thirty-one patients (39.8% of the total) underwent endotracheal intubation and mechanical ventilation and 62.6% of them died, compared to 17.7% of the non-intubated patients. Multivariable analysis confirmed a positive correlation between death and increased age (p = 0.05), surgical MDC (p = 0.007), number of microorganisms over the sample mean (p = 0.001), the presence of chronic diseases (p = 0.046), and intubation and mechanical ventilation (p < 0.0001). A positive correlation between intubation and antibiotic-resistant organisms (p = 0.003) was also found. HARIs are still a major public health problem and require constant surveillance due to their severe clinical outcome

Monolateral Ocular Tuberculosis in an Immunocompetent Patient: A Case Report

Abstract Introduction -A rare case of monolateral tubercular choroiditis in a 25 year old Bengali man without pulmonary involvement was reported

Merkel cell polyomavirus (MCPyV) in the context of Immunosuppression. Genetic analysis of noncoding control region (NCCR) variability among a HIV-1-positive population

Background: Since limited data are available about the prevalence of Merkel cell polyomavirus (MCPyV) and the genetic variability of its noncoding control region (NCCR) in the context of immunosuppression, this study aimed to investigate the distribution of MCPyV in anatomical sites other than the skin and the behavior of NCCR among an HIV-1-positive population. Methods: Urine, plasma, and rectal swabs specimens from a cohort of 66 HIV-1-positive patients were collected and subjected to quantitative real-time polymerase chain reaction (qPCR) for MCPyV DNA detection. MCPyV-positive samples were amplified by nested PCR targeting the NCCR, and NCCRs alignment was carried out to evaluate the occurrence of mutations and to identify putative binding sites for cellular factors. Results: MCPyV DNA was detected in 10/66 urine, in 7/66 plasma, and in 23/66 rectal samples, with a median value of 5 × 102 copies/mL, 1.5 × 102 copies/mL, and 2.3 × 103 copies/mL, respectively. NCCR sequence analysis revealed a high degree of homology with the MCC350 reference strain in urine, whereas transitions, transversions, and single or double deletions were observed in plasma and rectal swabs. In these latter samples, representative GTT and GTTGA insertions were also observed. Search for putative binding sites of cellular transcription factors showed that in several strains, deletions, insertions, or single base substitutions altered the NCCR canonical configuration. Conclusions: Sequencing analysis revealed the presence of numerous mutations in the NCCR, including insertions and deletions. Whether these mutations may have an impact on the pathogenic features of the virus remains to be determined. qPCR measured on average a low viral load in the specimens analyzed, with the exception of those with the GTTGA insertion

Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects