Prevalence of hepatitis E infection in HIV/HCV-coinfected patients in Spain (2012-2014)

Hepatitis E virus (HEV) has emerged as a relevant pathogen for HIV-infected patients. However, there is scarce data on HEV infection in HIV/HCV-coinfected individuals with advanced fibrosis, which seems to increase the risk of HEV infection and worsen the prognosis of liver disease. We aimed to determine the prevalence of anti-HEV antibodies, acute hepatitis E, resolved hepatitis E, and exposure to HEV in HIV/HCV-coinfected patients and to evaluate associations with clinical and epidemiological characteristics. We performed a cross-sectional study on 198 HIV/HCV-coinfected patients, 30 healthy controls and 36 HIV-monoinfected patients. We found a low concordance between techniques used for detection of anti-HEV antibodies (ELISA versus Immunoblot), particularly in HIV/HCV-coinfected patients. HIV/HCV-coinfected patients showed the highest prevalence of IgG against HEV, resolved hepatitis E, and exposure to HEV (19.2%, 17.2%, and 22.2% respectively). However, we did not find any samples positive for HEV-RNA nor significant differences between groups. Moreover, HIV/HCV-coinfected patients with CD4 T-cells <350 cells/mm3 had higher prevalence for anti-HEV IgG antibodies, resolved hepatitis E, and exposure to HEV than healthy controls or those with CD4 T-cells ≥ 350 cells/mm3 (p = 0.034, p = 0.035, and p = 0.053; respectively). In conclusion, HIV/HCV-coinfected patients in Spain have a high prevalence for IgG anti-HEV antibodies, resolved hepatitis E, and exposure to HEV; particularly patients with CD4+T-cells <350 cells/mm3.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by the Institute of Health Carlos III, ISCIII, Spanish Health Ministry (Grant n° RD06/0006/0035 and RD12/0017/0037) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF) and Foundation for Research and Prevention of AIDS in Spain (FIPSE). The RIS Cohort (CoRIS) is funded by the ISCIII through the Spanish AIDS Research Network (RIS C03/173 and RD12/0017/0018) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers grant numbers PI14/01094 and PI17/00657 to JB, PI14/01581, and PI17/00903 to JGG, PI14CIII/00011, and PI17CIII/00003 to SR), Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11–241). The RD16CIII/0002/0002, RD16/0025/0017, and RD16/0025/0018 projects also funded the study as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT15/00079 and INT16/00100.S

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

HIV and Mature Dendritic Cells: Trojan Exosomes Riding the Trojan Horse?

Exosomes are secreted cellular vesicles that can induce specific CD4+ T cell responses in vivo when they interact with competent antigen-presenting cells like mature dendritic cells (mDCs). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence of fusion events in search of adequate target cells. Here, we discuss recent data supporting this hypothesis, which further explains how DCs can capture and internalize retroviruses like HIV-1 in the absence of fusion events, leading to the productive infection of interacting CD4+ T cells and contributing to viral spread through a mechanism known as trans-infection. We suggest that HIV-1 can exploit an exosome antigen-dissemination pathway intrinsic to mDCs, allowing viral internalization and final trans-infection of CD4+ T cells. In contrast to previous reports that focus on the ability of immature DCs to capture HIV in the mucosa, this review emphasizes the outstanding role that mature DCs could have promoting trans-infection in the lymph node, underscoring a new potential viral dissemination pathway

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Isostructural M(RL)(2)(hfac)(2) complexes with RL=5-(4-[N-tert-butyl-N-aminoxyl]phenyl)pyrimidine

5-(4-(N-tert-Butyl-N-aminoxylphenyl)) pyrimidine (RL, 4PPN) forms crystallographically isostructural and isomorphic pseudo-octahedral M(RL)(2)(hfac)(2) complexes with M(hfac)(2), M = Zn, Cu, Ni, Co, and Mn. Multiple close contacts occur between sites of significant spin density of the organic radical units. Magnetic behavior of the Zn, Cu, Ni, Co complexes appears to involve multiple exchange pathways, with multiple close crystallographic contacts between sites that EPR (of 4PPN) indicates to have observable spin density. Powder EPR spectra at room temperature and low temperature are reported for each complex. Near room temperature, the magnetic moments of the complexes are roughly equal to those expected by a sum of non-interacting moments (two radicals plus ion). As temperature decreases, AFM exchange interactions become evident in all of the complexes. The closest fits to the magnetic data were found for a 1-D Heisenberg AFM chain model in the Zn(II) complex (J/k = (-)7 K), and for three-spin RL-M-RL exchange in the other complexes (J/k = (-)26 K, (-)3 K, (-) 6 K, for Cu(II), Ni(II), and Co(II) complexes, respectively). (C) 2008 Elsevier B.V. All rights reserved