60 results on '"Marc Noguera-Julian"'
Search Results
2. Gut resistome linked to sexual preference and HIV infection
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Elisa Rubio Garcia, Maria Casadellà, Mariona Parera, Jordi Vila, Roger Paredes, and Marc Noguera-Julian
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Gut resistome ,HIV infection ,Shotgun metagenomics ,Antimicrobial resistance ,Gut microbiome ,Microbiology ,QR1-502 - Abstract
Abstract Background People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have–sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition. Results Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories. Conclusions Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.
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- 2024
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3. Vaccination with an HIV T-cell immunogen induces alterations in the mouse gut microbiota
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Alessandra Borgognone, Aleix Elizalde-Torrent, Maria Casadellà, Luis Romero, Tuixent Escribà, Mariona Parera, Francesc Català-Moll, Marc Noguera-Julian, Christian Brander, Alex Olvera, and Roger Paredes
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Microbial ecology ,QR100-130 - Abstract
Abstract The gut microbiota is emerging as a crucial factor modulating vaccine responses; however, few studies have investigated if vaccines, in turn, can alter the microbiota and to what extent such changes may improve vaccine efficacy. To understand the effect of T-cell vaccination on the gut microbiome, we administered an HIV-1 T-cell immunogen (HTI arm) or PBS (control, Mock arm) to C57Bl/6 mice following a heterologous prime-boost scheme. The longitudinal dynamics of the mice gut microbiota was characterized by 16 S ribosomal RNA sequencing in fecal samples collected from cages, as well as from three gut sections (cecum, small and large intestine). Serum and spleen cells were obtained at the last time point of the study to assess immune correlates using IFNγ ELISPOT and cytokine Luminex® assays. Compared with Mock, HTI-vaccinated mice were enriched in Clostridiales genera (Eubacterium xylanophilum group, Roseburia and Ruminococcus) known as primary contributors of anti-inflammatory metabolites, such as short-chain fatty acids. Such shift was observed after the first HTI dose and remained throughout the study follow-up (18 weeks). However, the enriched Clostridiales genera were different between feces and gut sections. The abundance of bacteria enriched in vaccinated animals positively correlated with HTI-specific T-cell responses and a set of pro-inflammatory cytokines, such as IL-6. This longitudinal analysis indicates that, in mice, T-cell vaccination may promote an increase in gut bacteria known to produce anti-inflammatory molecules, which in turn correlate with proinflammatory cytokines, suggesting an adaptation of the gut microbial milieu to T-cell-induced systemic inflammation.
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- 2022
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4. Monitoring SARS-CoV-2 variant transitions using differences in diagnostic cycle threshold values of target genes
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Antoni E. Bordoy, Verónica Saludes, David Panisello Yagüe, Gemma Clarà, Laia Soler, Alexia Paris de León, Cristina Casañ, Ana Blanco-Suárez, Mercedes Guerrero-Murillo, Beatriz Rodríguez-Ponga, Marc Noguera-Julian, Francesc Català-Moll, Irina Pey, Maria Pilar Armengol, Maria Casadellà, Mariona Parera, Raquel Pluvinet, Lauro Sumoy, Bonaventura Clotet, Montserrat Giménez, Elisa Martró, Pere-Joan Cardona, and Ignacio Blanco
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Medicine ,Science - Abstract
Abstract Monitoring the emergence of new SARS-CoV-2 variants is important to detect potential risks of increased transmission or disease severity. We investigated the identification of SARS-CoV-2 variants from real-time reverse transcriptase polymerase chain reaction (RT-PCR) routine diagnostics data. Cycle threshold (Ct) values of positive samples were collected from April 2021 to January 2022 in the Northern Metropolitan Area of Barcelona (n = 15,254). Viral lineage identification from whole genome sequencing (WGS) was available for 4618 (30.3%) of these samples. Pairwise differences in the Ct values between gene targets (ΔCt) were analyzed for variants of concern or interest circulating in our area. A specific delay in the Ct of the N-gene compared to the RdRp-gene (ΔCtNR) was observed for Alpha, Delta, Eta and Omicron. Temporal differences in ΔCtNR correlated with the dynamics of viral replacement of Alpha by Delta and of Delta by Omicron according to WGS results. Using ΔCtNR, prediction of new variants of concern at early stages of circulation was achieved with high sensitivity and specificity (91.1% and 97.8% for Delta; 98.5% and 90.8% for Omicron). Thus, tracking population-wide trends in ΔCt values obtained from routine diagnostics testing in combination with WGS could be useful for real-time management and response to local epidemics.
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- 2022
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5. Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study
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José Ramón Santos, Maria Casadellà, Marc Noguera-Julian, Rafael Micán-Rivera, Pere Domingo, Antonio Antela, Joaquin Portilla, Jesús Sanz, Marta Montero-Alonso, Jordi Navarro, Mar Masiá, Nieves Valcarce-Pardeiro, Antonio Ocampo, Laura Pérez-Martínez, Coral García-Vallecillos, María Jesús Vivancos, Arkaitz Imaz, José Antonio Iribarren, José Hernández-Quero, Judit Villar-García, Pilar Barrufet, Roger Paredes, INSTINCT study group, Mariona Perera, Anna Chamorro, Cristina Miranda, Nástor Sánchez, Anna Garcı́á, Núria Pérez, Juan González Garcı́á, María del Mar Gutiérrez, María Gracia Mateo, Elena Losada, Sergio Reus, Vicente Boix, Diego Torrús, Esperanza Merino, Angela Gutiérrez Liarte, Adrià Curran, Félix Gutiérrez, Anna Mariño Callejo, Alvarez Diaz Hortensia, Antonio Ocampo Hermida, Celia Miralles, Laura Labajo Leal, Guillermo Pousada, José Ramon Blanco, José Antonio Oteo, Ibarra Valvanera, Mercedes Sanz, Luis Metola, Juan Pascua, Daniel Podzamczer, Camila Piatti, Maialen Ibarguren, Laia Arbones, Marta Ruiz, Sara Cervanntes, Helena Pera, Jessica Toro, Nuria Perez-Alvarez, and Anna Garcia
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HIV ,integrase strand transfer inhibitors (INSTI) ,real-world study ,raltegravir ,elvitegravir ,dolutegravir ,Microbiology ,QR1-502 - Abstract
IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir
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- 2023
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6. Impact of hybrid immunity booster vaccination and Omicron breakthrough infection on SARS-CoV-2 VOCs cross-neutralization
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Edwards Pradenas, Silvia Marfil, Víctor Urrea, Macedonia Trigueros, Tetyana Pidkova, Anna Pons-Grífols, Raquel Ortiz, Carla Rovirosa, Ferran Tarrés-Freixas, Carmen Aguilar-Gurrieri, Ruth Toledo, Anna Chamorro, Marc Noguera-Julian, Lourdes Mateu, Ignacio Blanco, Eulàlia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Benjamin Trinité, and Julià Blanco
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Biochemistry ,Immune response ,Microbiology ,Science - Abstract
Summary: The elicitation of cross-variant neutralizing antibodies against SARS-CoV-2 represents a major goal for current COVID-19 vaccine strategies. Additionally, natural infection may also contribute to broaden neutralizing responses. To assess the contribution of vaccines and natural infection, we cross-sectionally analyzed plasma neutralization titers of six groups of individuals, organized according to the number of vaccines they received and their SARS-CoV-2 infection history. Two doses of vaccine had a limited capacity to generate cross-neutralizing antibodies against Omicron variants of concern (VOCs) in uninfected individuals, but efficiently synergized with previous natural immunization in convalescent individuals. In contrast, booster dose had a critical impact on broadening the cross-neutralizing response in uninfected individuals, to level similar to hybrid immunity, while still improving cross-neutralizing responses in convalescent individuals. Omicron breakthrough infection improved cross-neutralization of Omicron subvariants in non-previously infected vaccinated individuals. Therefore, ancestral Spike-based immunization, via infection or vaccination, contributes to broaden SARS-CoV-2 humoral immunity.
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- 2023
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7. Gut microbiome signatures linked to HIV-1 reservoir size and viremia control
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Alessandra Borgognone, Marc Noguera-Julian, Bruna Oriol, Laura Noël-Romas, Marta Ruiz-Riol, Yolanda Guillén, Mariona Parera, Maria Casadellà, Clara Duran, Maria C. Puertas, Francesc Català-Moll, Marlon De Leon, Samantha Knodel, Kenzie Birse, Christian Manzardo, José M. Miró, Bonaventura Clotet, Javier Martinez-Picado, José Moltó, Beatriz Mothe, Adam Burgener, Christian Brander, Roger Paredes, and the BCN02 Study Group
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HIV-1 post-treatment control ,Gut microbiome ,Therapeutic HIV-1 vaccine ,Viral reservoir size ,Microbiome-based predictive biomarker ,Microbial ecology ,QR100-130 - Abstract
Abstract Background The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Results Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridial es. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. Conclusions The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. Video abstract
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- 2022
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8. Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels
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Aleix Elizalde-Torrent, Alessandra Borgognone, Maria Casadellà, Luis Romero-Martin, Tuixent Escribà, Mariona Parera, Yaiza Rosales-Salgado, Jorge Díaz-Pedroza, Francesc Català-Moll, Marc Noguera-Julian, Christian Brander, Roger Paredes, and Alex Olvera
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microbiota ,HIV ,vaccine ,T-cell ,IFNγ ,IL-22 ,Medicine - Abstract
Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.
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- 2023
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9. Probiotic effects on immunity and microbiome in HIV-1 discordant patients
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Carlos Blázquez-Bondia, Mariona Parera, Francesc Català-Moll, Maria Casadellà, Aleix Elizalde-Torrent, Meritxell Aguiló, Jordi Espadaler-Mazo, José Ramon Santos, Roger Paredes, and Marc Noguera-Julian
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probiotics ,prebiotics ,synbiotics ,HIV ,immune reconstitution ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundSome HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution.SettingRECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vallès, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts
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- 2022
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10. The gut microbiome in patients with chronic lymphocytic leukemia
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Tereza Faitová, Rebecka Svanberg, Caspar da Cunha-Bang, Emma E. Ilett, Mette Jørgensen, Marc Noguera-Julian, Roger Paredes, Cameron R. MacPherson, and Carsten U. Niemann
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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11. Performance of SARS-CoV-2 Antigen-Detecting Rapid Diagnostic Tests for Omicron and Other Variants of Concern
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Dàlia Raïch-Regué, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Edwards Pradenas, Eva Riveira-Muñoz, Neus Giménez, Assumpta Carabaza, Francesc Giménez, Verónica Saludes, Elisa Martró, Neus Robert, Ignacio Blanco, Roger Paredes, Lidia Ruiz, Ester Ballana, Bonaventura Clotet, Julià Blanco, and Nuria Izquierdo-Useros
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SARS-CoV-2 ,diagnosis ,antigen-detecting rapid diagnostic tests ,variants of concern ,nucleocapsid (N) ,Microbiology ,QR1-502 - Abstract
The SARS-CoV-2 antigen-detecting rapid diagnostic test (Ag-RDTs) is an easy-to-use diagnostic tool to identify the contagious individuals and reduce the new infections. However, to be effective, Ag-RDTs require the detection of distinct variants of concern (VOC) with high analytical sensitivity. Here, we found that the VOC diverge at the nucleocapsid protein used by four commercial Ag-RDTs for the viral detection. Relative to the original D614G variant, there was a 10-fold loss of detection for the Delta and Alpha variants in certain Ag-RDTs, a reduction above the threshold required to isolate the viable virus. However, Beta and Omicron variants did not lose the detection capacity. As the new VOC arise, successful contact tracing requires continuous monitoring of Ag-RDTs performance.
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- 2022
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12. Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome
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Ramtin Zargari Marandi, Mette Jørgensen, Emma Elizabeth Ilett, Jens Christian Nørgaard, Marc Noguera-Julian, Roger Paredes, Jens D. Lundgren, Henrik Sengeløv, and Cameron Ross MacPherson
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human gut microbiome ,aGvHD biomarkers ,metagenome-wide association ,next generation sequencing ,pre-transplant screening ,taxonomic assignment ,Cytology ,QH573-671 - Abstract
Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore. Microbial abundance profiles were estimated using ensembles of Kaiju, Kraken2, and DeepMicrobes calls followed by dimensionality reduction. The area under the curve (AUC) was used to evaluate classification of the samples (aGvHD vs. none) using an elastic net to test the relevance of metagenomic data. Clinical data included the underlying disease (leukemia vs. other hematological malignancies), recipient age, and sex. Among 172 aHSCT patients of whom 42 developed aGVHD post transplantation, a total of 181 pre-transplant tool samples were analyzed. The top performing model predicting risk of aGVHD included a reduced species profile (AUC = 0.672). Beta diversity (37% in Jaccard’s Nestedness by mean fold change, p < 0.05) was lower in those developing aGvHD. Ten bacterial species including Prevotella and Eggerthella genera were consistently found to associate with aGvHD in indicator species analysis, as well as relief and impurity-based algorithms. The findings support the hypothesis on potential associations between gut microbiota and aGvHD based on a data-driven approach to MWAS. This highlights the need and relevance of routine stool collection for the discovery of novel biomarkers.
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- 2022
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13. Evolution of the gut microbiome following acute HIV-1 infection
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Muntsa Rocafort, Marc Noguera-Julian, Javier Rivera, Lucía Pastor, Yolanda Guillén, Jost Langhorst, Mariona Parera, Inacio Mandomando, Jorge Carrillo, Víctor Urrea, Cristina Rodríguez, Maria Casadellà, Maria Luz Calle, Bonaventura Clotet, Julià Blanco, Denise Naniche, and Roger Paredes
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Microbiome ,HIV-1 ,acute HIV-1 infection ,HIV-1 pathogenesis ,AIDS ,Microbial ecology ,QR100-130 - Abstract
Abstract Background In rhesus macaques, simian immunodeficiency virus infection is followed by expansion of enteric viruses but has a limited impact on the gut bacteriome. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection (RHI) and 54 HIV-1-negative controls for 9–18 months and compared them with 98 chronically HIV-1-infected subjects treated with antiretrovirals (n = 27) or not (n = 71). Results We show that RHI is followed by increased fecal adenovirus shedding, which persists during chronic HIV-1 infection and does not resolve with ART. Recent HIV-1 infection is also followed by transient non-HIV-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome—featuring depletion of Akkermansia, Anaerovibrio, Bifidobacterium, and Clostridium—previously associated with chronic inflammation, CD8+ T cell anergy, and metabolic disorders, can be eventually identified in chronically HIV-1-infected subjects. Conclusions Recent HIV-1 infection is associated with increased fecal shedding of eukaryotic viruses, transient loss of bacterial taxonomic richness, and long-term reductions in microbial gene richness. An HIV-1-associated microbiome signature only becomes evident in chronically HIV-1-infected subjects.
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- 2019
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14. Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect After a Drug Repurposing Screen
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Jordi Rodon, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Roger Paredes, Lourdes Mateu, Carles Quiñones, Carles Perez, Itziar Erkizia, Ignacio Blanco, Alfonso Valencia, Víctor Guallar, Jorge Carrillo, Julià Blanco, Joaquim Segalés, Bonaventura Clotet, Júlia Vergara-Alert, and Nuria Izquierdo-Useros
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SARS-CoV-2 ,antivirals ,plitidepsin ,synergy ,viral entry ,Therapeutics. Pharmacology ,RM1-950 - Abstract
There is an urgent need to identify therapeutics for the treatment of Coronavirus disease 2019 (COVID-19). Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18 % had an IC50 below 25 µM or 102 IU/ml. These included plitidepsin, novel cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate, camostat along the well-known remdesivir and chloroquine derivatives. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell—type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials.
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- 2021
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15. Yaws re-emergence and bacterial drug resistance selection after mass administration of azithromycin: a genomic epidemiology investigation
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Mathew A Beale, PhD, Marc Noguera-Julian, PhD, Charmie Godornes, BSc, Maria Casadellà, PhD, Camila González-Beiras, PhD, Mariona Parera, BSc, August Kapa Jnr, BSc, Wendy Houinei, MPH, James Wangi, MPH, Marc Corbacho-Monne, MBBS, Roger Paredes, PhD, Fernando Gonzalez-Candelas, ProfPhD, Michael Marks, PhD, Sheila A Lukehart, ProfPhD, Nicholas R Thomson, ProfPhD, and Oriol Mitjà, PhD
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Medicine (General) ,R5-920 ,Microbiology ,QR1-502 - Abstract
Summary: Background: In a longitudinal study assessing the WHO strategy for yaws eradication using mass azithromycin treatment, we observed resurgence of yaws cases with dominance of a single JG8 sequence type and emergence of azithromycin-resistant Treponema pallidum subspecies pertenue (T p pertenue). Here, we analyse genomic changes in the bacterial population using samples collected during the study. Methods: We did whole bacterial genome sequencing directly on DNA extracted from 37 skin lesion swabs collected from patients on Lihir Island, Papua New Guinea, between April 1, 2013, and Nov 1, 2016. We produced phylogenies and correlated these with spatiotemporal information to investigate the source of new cases and the emergence of five macrolide-resistant cases. We used deep amplicon sequencing of surveillance samples to assess the presence of minority macrolide-resistant populations. Findings: We recovered 20 whole T p pertenue genomes, and phylogenetic analysis showed that the re-emerging JG8 sequence type was composed of three bacterial sublineages characterised by distinct spatiotemporal patterns. Of five patients with resistant T p pertenue, all epidemiologically linked, we recovered genomes from three and found no variants. Deep sequencing showed that before treatment, the index patient had fixed macrolide-sensitive T p pertenue, whereas the post-treatment sample had a fixed resistant genotype, as did three of four contact cases. Interpretation: In this study, re-emergence of yaws cases was polyphyletic, indicating multiple epidemiological sources. However, given the genomic and epidemiological linkage of resistant cases and the rarity of resistance alleles in the general population, azithromycin resistance is likely to have evolved only once in this study, followed by onward dissemination. Funding: Wellcome and Provincial Deputation of Barcelona.
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- 2020
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16. Richer gut microbiota with distinct metabolic profile in HIV infected Elite Controllers
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Jan Vesterbacka, Javier Rivera, Kajsa Noyan, Mariona Parera, Ujjwal Neogi, Malu Calle, Roger Paredes, Anders Sönnerborg, Marc Noguera-Julian, and Piotr Nowak
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Medicine ,Science - Abstract
Abstract Gut microbiota dysbiosis features progressive HIV infection and is a potential target for intervention. Herein, we explored the microbiome of 16 elite controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative controls. We found that the number of observed genera and richness indices in fecal microbiota were significantly higher in EC versus naive. Genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were more abundant in EC, whereas Blautia and Anaerostipes were depleted. Additionally, carbohydrate metabolism and secondary bile acid synthesis pathway related genes were less represented in EC. Conversely, fatty acid metabolism, PPAR-signalling and lipid biosynthesis proteins pathways were enriched in EC vs naive. The kynurenine pathway of tryptophan metabolism was altered during progressive HIV infection, and inversely associated with microbiota richness. In conclusion, EC have richer gut microbiota than untreated HIV patients, with unique bacterial signatures and a distinct metabolic profile which may contribute to control of HIV.
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- 2017
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17. Gut Microbiota Linked to Sexual Preference and HIV Infection
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Marc Noguera-Julian, Muntsa Rocafort, Yolanda Guillén, Javier Rivera, Maria Casadellà, Piotr Nowak, Falk Hildebrand, Georg Zeller, Mariona Parera, Rocío Bellido, Cristina Rodríguez, Jorge Carrillo, Beatriz Mothe, Josep Coll, Isabel Bravo, Carla Estany, Cristina Herrero, Jorge Saz, Guillem Sirera, Ariadna Torrela, Jordi Navarro, Manel Crespo, Christian Brander, Eugènia Negredo, Julià Blanco, Francisco Guarner, Maria Luz Calle, Peer Bork, Anders Sönnerborg, Bonaventura Clotet, and Roger Paredes
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HIV-1 ,Microbiome ,Microbiota ,16S rDNA ,Prevotella ,Bacteroides ,Medicine ,Medicine (General) ,R5-920 - Abstract
The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction.
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- 2016
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18. SARS-CoV-2 Consensus-Sequence and Matching Overlapping Peptides Design for COVID19 Immune Studies and Vaccine Development
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Alex Olvera, Marc Noguera-Julian, Athina Kilpelainen, Luis Romero-Martín, Julia G. Prado, and Christian Brander
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COVID-19 ,SARS-CoV-2 ,consensus sequence ,T cell immunity ,overlapping peptides set ,Medicine - Abstract
Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to test immune responses in exposed and infected individuals at the population level. To accelerate immune studies in SARS-CoV-2 infection, we here describe a SARS-CoV-2 2020 consensus sequence (CoV-2-cons) which is based on more than 1700 viral genome entries in NCBI and encompasses all described SARS-CoV-2 open reading frames (ORF), including recently described frame-shifted and length variant ORF. Based on these sequences, we created curated overlapping peptide (OLP) lists containing between 1500 to 3000 peptides of 15 and 18 amino acids in length, overlapping by 10 or 11 residues, as ideal tools for the assessment of SARS-CoV-2-specific T cell immunity. In addition, CoV-2-cons sequence entropy values are presented along with variant sequences to provide increased coverage of the most variable sections of the viral genome. The identification of conserved protein fragments across the coronavirus family and the corresponding OLP facilitate the identification of T cells potentially cross-reactive with related viruses. This new CoV-2-cons sequence, together with the peptides sets, should provide the basis for SARS-CoV-2 antigen synthesis to facilitate comparability between ex-vivo immune analyses and help to accelerate research on SARS-CoV-2 immunity and vaccine development.
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- 2020
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19. Dry Panels Supporting External Quality Assessment Programs for Next Generation Sequencing-Based HIV Drug Resistance Testing
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Marc Noguera-Julian, Emma R. Lee, Robert W. Shafer, Rami Kantor, and Hezhao Ji
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HIV ,drug resistance testing ,next generation sequencing ,external quality assessment ,dry panel ,Microbiology ,QR1-502 - Abstract
External quality assessment (EQA) is a keystone element in the validation and implementation of next generation sequencing (NGS)-based HIV drug resistance testing (DRT). Software validation and evaluation is a critical element in NGS EQA programs. While the development, sharing, and adoption of wet lab protocols is coupled with the increasing access to NGS technology worldwide, rendering it easy to produce NGS data for HIV-DRT, bioinformatic data analysis remains a bottleneck for most of the diagnostic laboratories. Several computational tools have been made available, via free or commercial sources, to automate the conversion of raw NGS data into an actionable clinical report. Although different software platforms yield equivalent results when identical raw NGS datasets are analyzed for variations at higher abundance, discrepancies arise when variations at lower frequencies are considered. This implies that validation and performance assessment of the bioinformatics tools applied in NGS HIV-DRT is critical, and the origins of the observed discrepancies should be determined. Well-characterized reference NGS datasets with ground truth on the genotype composition at all examined loci and the exact frequencies of HIV variations they may harbor, so-called dry panels, would be essential in such cases. The strategic design and construction of such panels are challenging but imperative tasks in support of EQA programs for NGS-based HIV-DRT and the validation of relevant bioinformatics tools. Here, we present criteria that can guide the design of such dry panels, which were discussed in the Second International Winnipeg Symposium themed for EQA strategies for NGS HIVDR assays.
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- 2020
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20. Multi-Laboratory Comparison of Next-Generation to Sanger-Based Sequencing for HIV-1 Drug Resistance Genotyping
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Neil T. Parkin, Santiago Avila-Rios, David F. Bibby, Chanson J. Brumme, Susan H. Eshleman, P. Richard Harrigan, Mark Howison, Gillian Hunt, Hezhao Ji, Rami Kantor, Johanna Ledwaba, Emma R. Lee, Margarita Matías-Florentino, Jean L. Mbisa, Marc Noguera-Julian, Roger Paredes, Vanessa Rivera-Amill, Ronald Swanstrom, Daniel J. Zaccaro, Yinfeng Zhang, Shuntai Zhou, and Cheryl Jennings
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HIV-1 ,drug resistance ,genotyping ,NGS ,Microbiology ,QR1-502 - Abstract
Next-generation sequencing (NGS) is increasingly used for HIV-1 drug resistance genotyping. NGS methods have the potential for a more sensitive detection of low-abundance variants (LAV) compared to standard Sanger sequencing (SS) methods. A standardized threshold for reporting LAV that generates data comparable to those derived from SS is needed to allow for the comparability of data from laboratories using NGS and SS. Ten HIV-1 specimens were tested in ten laboratories using Illumina MiSeq-based methods. The consensus sequences for each specimen using LAV thresholds of 5%, 10%, 15%, and 20% were compared to each other and to the consensus of the SS sequences (protease 4–99; reverse transcriptase 38–247). The concordance among laboratories’ sequences at different thresholds was evaluated by pairwise sequence comparisons. NGS sequences generated using the 20% threshold were the most similar to the SS consensus (average 99.6% identity, range 96.1–100%), compared to 15% (99.4%, 88.5–100%), 10% (99.2%, 87.4–100%), or 5% (98.5%, 86.4–100%). The average sequence identity between laboratories using thresholds of 20%, 15%, 10%, and 5% was 99.1%, 98.7%, 98.3%, and 97.3%, respectively. Using the 20% threshold, we observed an excellent agreement between NGS and SS, but significant differences at lower thresholds. Understanding how variation in NGS methods influences sequence quality is essential for NGS-based HIV-1 drug resistance genotyping.
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- 2020
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21. Are We Ready for NGS HIV Drug Resistance Testing? The Second 'Winnipeg Consensus' Symposium
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Hezhao Ji, Paul Sandstrom, Roger Paredes, P. Richard Harrigan, Chanson J. Brumme, Santiago Avila Rios, Marc Noguera-Julian, Neil Parkin, and Rami Kantor
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NGS ,HIV drug resistance testing ,Winnipeg Consensus ,symposium ,Microbiology ,QR1-502 - Abstract
HIV drug resistance is a major global challenge to successful and sustainable antiretroviral therapy. Next-generation sequencing (NGS)-based HIV drug resistance (HIVDR) assays enable more sensitive and quantitative detection of drug-resistance-associated mutations (DRMs) and outperform Sanger sequencing approaches in detecting lower abundance resistance mutations. While NGS is likely to become the new standard for routine HIVDR testing, many technical and knowledge gaps remain to be resolved before its generalized adoption in regular clinical care, public health, and research. Recognizing this, we conceived and launched an international symposium series on NGS HIVDR, to bring together leading experts in the field to address these issues through in-depth discussions and brainstorming. Following the first symposium in 2018 (Winnipeg, MB Canada, 21–22 February, 2018), a second “Winnipeg Consensus” symposium was held in September 2019 in Winnipeg, Canada, and was focused on external quality assurance strategies for NGS HIVDR assays. In this paper, we summarize this second symposium’s goals and highlights.
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- 2020
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22. Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
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Carolina Beltran-Pavez, Carolina B Ferreira, Alberto Merino-Mansilla, Amanda Fabra-Garcia, Maria Casadella, Marc Noguera-Julian, Roger Paredes, Alex Olvera, Isabel Haro, Christian Brander, Felipe Garcia, Jose M Gatell, Eloisa Yuste, and Victor Sanchez-Merino
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Medicine ,Science - Abstract
Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging. Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region). Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop. Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env. Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies. In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env. While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region. Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
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- 2018
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23. Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro
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Alex Olvera, Javier P. Martinez, Maria Casadellà, Anuska Llano, Míriam Rosás, Beatriz Mothe, Marta Ruiz-Riol, Gemma Arsequell, Gregorio Valencia, Marc Noguera-Julian, Roger Paredes, Andreas Meyerhans, and Christian Brander
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human immunodeficiency virus-1 ,benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside ,O-glycosylation ,viral outgrowth ,replication ,infectivity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Glycosylation of host and viral proteins is an important posttranslational modification needed to ensure correct function of glycoproteins. For this reason, we asked whether inhibition of O-glycosylation during human immunodeficiency virus (HIV) in vitro replication could affect HIV infectivity and replication rates. We used benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside (BAGN), a compound that has been widely used to inhibit O-glycosylation in several cell lines. Pretreatment and culture of PHA-blast target cells with BAGN increased the percentage of HIV-infected cells (7.6-fold, p = 0.0115), the per-cell amount of HIV p24 protein (1.3-fold, p = 0.2475), and the viral particles in culture supernatants (7.1-fold, p = 0.0029) compared to BAGN-free cultures. Initiating infection with virus previously grown in the presence of BAGN further increased percentage of infected cells (30-fold, p
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- 2018
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24. HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique.
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María Rupérez, Marc Noguera-Julian, Raquel González, Sonia Maculuve, Rocío Bellido, Anifa Vala, Cristina Rodríguez, Esperança Sevene, Roger Paredes, and Clara Menéndez
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Medicine ,Science - Abstract
Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care.To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART).Samples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery.Ninety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts
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- 2018
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25. Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B.
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Miriam Rosás-Umbert, Beatriz Mothe, Marc Noguera-Julian, Rocío Bellido, Maria C Puertas, Jorge Carrillo, C Rodriguez, Núria Perez-Alvarez, Patricia Cobarsí, Carmen E Gomez, Mariano Esteban, Jose Luis Jímenez, Felipe García, Julià Blanco, Javier Martinez-Picado, Roger Paredes, and Christian Brander
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Medicine ,Science - Abstract
The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches.
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- 2017
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26. Plasma HIV-1 Tropism and the Risk of Short-Term Clinical Progression to AIDS or Death.
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Maria Casadellà, Alessandro Cozzi-Lepri, Andrew Phillips, Marc Noguera-Julian, Markus Bickel, Dalibor Sedlacek, Kai Zilmer, Bonaventura Clotet, Jens D Lundgren, Roger Paredes, and EuroSIDA in EuroCOORD
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Medicine ,Science - Abstract
OBJECTIVETo investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management.DESIGNNested case-control study within the EuroSIDA cohort.METHODSCases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling.RESULTSThe study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, pCONCLUSIONSThe predictive role of plasma tropism determined using 454 sequencing in the context of people receiving cART with detectable VL is not helpful to identify subjects at higher risk for clinical progression to AIDS or death.
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- 2017
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27. Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.
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Jose Manuel Vazquez-Guillen, Gerardo C Palacios-Saucedo, Lydia G Rivera-Morales, Jorge Garcia-Campos, Rocio Ortiz-Lopez, Marc Noguera-Julian, Roger Paredes, Herlinda J Vielma-Ramirez, Teresa J Ramirez, Marcelino Chavez-Garcia, Paulo Lopez-Guillen, Evangelina Briones-Lara, Luz M Sanchez-Sanchez, Carlos A Vazquez-Martinez, and Cristina Rodriguez-Padilla
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Medicine ,Science - Abstract
Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (
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- 2016
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28. Decreased phenotypic susceptibility to etravirine in patients with predicted genotypic sensitivity.
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Eva Agneskog, Piotr Nowak, Catharina Maijgren Steffensson, Maria Casadellà, Marc Noguera-Julian, Roger Paredes, Clas F R Källander, and Anders Sönnerborg
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Medicine ,Science - Abstract
BACKGROUND: A sensitive, phenotypic reverse transcriptase (RT)-based drug susceptibility assay for the detection of etravirine (ETR) resistance in patient isolates was developed and compared with the results from direct sequencing and ultra-deep pyrosequencing (UDPS). METHODS: Samples were obtained from 15 patients with antiretroviral therapy (ART) failure and from five non-nucleoside reverse transcriptase inhibitor (NNRTI)-naïve patients of whom four were infected by an NNRTI-resistant strain (transmitted drug resistance, TDR). In five patients, two consecutive samples (a and b) were taken for follow up of the virological response. HIV-1 RT was purified and drug susceptibility (IC50) to ETR was estimated. Direct sequencing was performed in all samples and UDPS in samples from nine patients. RESULTS: Increased IC50 to ETR was found in samples from 13 patients where direct sequencing predicted resistance in only four. UDPS identified additional (N = 11) NNRTI resistance associated mutations (RAMs) in six of nine tested patients. During early failure, IC50 increases were observed in three of six patients without any ETR-RAMs detected by direct sequencing. In further two patients, who stopped NNRTI before sampling, increased IC50 values were found shortly after, despite absence of ETR-RAMs. In two patients who had stopped NNRTI for >1 year, a concordance between phenotype and genotypes was found. Two patients with TDR had increased IC50 despite no ETR-RAMs were detected by direct sequencing. UDPS revealed additional ETR-RAMs in four patients with a discrepancy between phenotype and direct sequencing. CONCLUSIONS: The RT-based phenotypic assay showed decreased ETR susceptibility in patients where direct sequencing predicted ETR-sensitive virus. This increased phenotypic sensitivity was to a large extent supported by UDPS and treatment history. Our method could be valuable for further studies on the phenotypic kinetics of NNRTI resistance. The clinical relevance remains to be studied in larger patient-populations.
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- 2014
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29. HIV-1 tropism testing in subjects achieving undetectable HIV-1 RNA: diagnostic accuracy, viral evolution and compartmentalization.
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Christian Pou, Francisco M Codoñer, Alexander Thielen, Rocío Bellido, Susana Pérez-Álvarez, Cecilia Cabrera, Judith Dalmau, Marta Curriu, Yolanda Lie, Marc Noguera-Julian, Jordi Puig, Javier Martínez-Picado, Julià Blanco, Eoin Coakley, Martin Däumer, Bonaventura Clotet, and Roger Paredes
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Medicine ,Science - Abstract
BACKGROUND: Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. METHODS & RESULTS: We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA
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- 2013
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30. Author Correction to: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells
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Daniel Perez-Zsolt, Jordana Muñoz-Basagoiti, Jordi Rodon, Marc Elosua-Bayes, Dàlia Raïch-Regué, Cristina Risco, Martin Sachse, Maria Pino, Sanjeev Gumber, Mirko Paiardini, Jakub Chojnacki, Itziar Erkizia, Xabier Muñiz-Trabudua, Ester Ballana, Eva Riveira-Muñoz, Marc Noguera-Julian, Roger Paredes, Benjamin Trinité, Ferran Tarrés-Freixas, Ignacio Blanco, Victor Guallar, Jorge Carrillo, Julià Blanco, Amalio Telenti, Holger Heyn, Joaquim Segalés, Bonaventura Clotet, Javier Martinez-Picado, Júlia Vergara-Alert, and Nuria Izquierdo-Useros
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Mechanisms of disease ,Infectious Diseases ,Immunology ,Infectious diseases ,Immunology and Allergy - Abstract
Correction to: https://doi.org/10.1038/s41423-021-00794-6; http://hdl.handle.net/10261/257710, In the version of this correspondence initially published, one of the SARS-CoV-2 variants used in Fig. 1B, which was originally described in the article as the SARS-CoV-2 variant ‘B.1.1.248.2 Gamma’, is actually the ‘P.2 Zeta’ SARS-CoV-2 variant of interest. The GISAID accession ID EPI_ISL_1831696 provided is correct, but it belongs to the Zeta variant. The results and conclusions are not affected by this unintentional inaccuracy.
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- 2022
31. Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection
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Edwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Ferran Tarrés-Freixas, Raquel Ortiz, Carla Rovirosa, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Marc Noguera-Julian, Jorge Carrillo, Roger Paredes, Lourdes Mateu, Anna Chamorro, Ruth Toledo, Marta Massanella, Bonaventura Clotet, Julià Blanco, Producció Animal, Sanitat Animal, and Barcelona Supercomputing Center
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Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,Adult ,Male ,COVID-19 Vaccines ,half-life ,severity ,Acute respiratory syndrome, Severe ,Neutralizing antibodies ,variants of concern ,Antibodies, Viral ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Durability ,Severity ,Article ,Young Adult ,Humans ,neutralizing antibodies ,Humoral response ,Longitudinal Studies ,Prospective Studies ,SARS-CoV-2 (Malaltia) ,Aged ,Variants of concern ,B-Lymphocytes ,pseudovirus ,SARS-CoV-2 ,SARS-CoV-2 disease ,Vaccination ,Pseudovirus ,COVID-19 ,Middle Aged ,Half-life ,Antibodies, Neutralizing ,Kinetics ,Treatment Outcome ,B cell memory ,Spike Glycoprotein, Coronavirus ,durability ,Female ,Immunologic Memory ,humoral response ,Follow-Up Studies - Abstract
To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Long-term neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses., Graphical abstract, Pradenas and Trinité et al. analyze the kinetics of neutralizing antibodies in response to natural SARS-CoV-2 infection and evaluate the long-term (beyond 1 year) stability and breadth of the neutralizing response before subsequent vaccination.
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- 2022
32. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Infection and Humoral Responses Against Different Variants of Concern in Domestic Pet Animals and Stray Cats from North-Eastern Spain
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Leira Fernández‐Bastit, Silvia Marfil, Edwards Pradenas, Rosa Valle, Núria Roca, Jordi Rodon, Lola Pailler‐García, Benjamin Trinité, Mariona Parera, Marc Noguera‐Julian, Jaume Martorell, Nuria Izquierdo‐Useros, Jorge Carrillo, Bonaventura Clotet, Julià Blanco, Júlia Vergara‐Alert, Joaquim Segalés, Producció Animal, and Sanitat Animal
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Coronavirus disease 2019 (COVID-19) ,Variants of concern (VOCs) ,General Veterinary ,General Immunology and Microbiology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Stray cats ,General Medicine ,Pets ,Zoonotic transmission - Abstract
Altres ajuts: acords transformatius de la UAB Altres ajuts: BBVA Foundation; Grifols; National Agency for Research and Development of Chile, Grant/Award Number: 72180406; La Marató TV3, Grant/Award Number: 342/C/2021 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19) pandemic in humans, is able to infect several domestic, captive and wildlife animal species. Since reverse zoonotic transmission to pets has been demonstrated, it is crucial to determine their role in the epidemiology of the disease to prevent further spillover events and major spreads of SARS-CoV-2. In the present study, we determined the presence of virus and the seroprevalence to SARS-CoV-2, as well as the levels of neutralizing antibodies (nAbs) against several variants of concern (VOCs) in pets (cats, dogs and ferrets) and stray cats from North-Eastern of Spain. We confirmed that cats and dogs can be infected by different VOCs of SARS-CoV-2 and, together with ferrets, are able to develop nAbs against the ancestral (B.1), Alpha (B.1.1.7), Beta (B.1.315), Delta (B.1.617.2) and Omicron (BA.1) variants, with lower titres against the latest in dogs and cats, but not in ferrets. Although the prevalence of active SARS-CoV-2 infection measured as direct viral RNA detection was low (0.3%), presence of nAbs in pets living in COVID-19 positive households was relatively high (close to 25% in cats, 10% in dogs and 40% in ferrets). It is essential to continue monitoring SARS-CoV-2 infections in these animals due to their frequent contact with human populations, and we cannot discard the probability of a higher animal susceptibility to new potential SARS-CoV-2 VOCs.
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- 2022
33. Performance of 16S Metagenomic Profiling in Formalin-Fixed Paraffin-Embedded versus Fresh-Frozen Colorectal Cancer Tissues
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Roger Paredes, Marc Noguera-Julian, Lidia Alonso, Roberta Fasani, Alessandra Borgognone, Garazi Serna, Lidia Sanchez, Mariona Parera, Paolo Nuciforo, Francesc Català-Moll, Institut Català de la Salut, [Borgognone A, Parera M, Català-Moll F] IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. [Serna G, Alonso L, Sanchez L, Fasani R, Nuciforo P] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Noguera-Julian M] IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. Faculty of Medicine, University of Vic–Central University of Catalonia (UVic–UCC), Vic, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cancer Research ,fenómenos microbiológicos::microbiota::microbiota intestinal [FENÓMENOS Y PROCESOS] ,Recte - Càncer - Aspectes genètics ,Firmicutes ,microbiome ,Còlon - Càncer - Aspectes genètics ,colorectal cancer ,Computational biology ,FFPE ,Article ,Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES] ,Intestins - Microbiologia ,Microbiome ,RC254-282 ,Microbiological Phenomena::Microbiota::Gastrointestinal Microbiome [PHENOMENA AND PROCESSES] ,Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology::Genomics [DISCIPLINES AND OCCUPATIONS] ,biology ,Bacteroidetes ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Fusobacteria ,16S gene sequencing ,biology.organism_classification ,neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES] ,Rhodobacterales ,Oncology ,Fusobacterium ,Metagenomics ,disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::biología::biología computacional::genómica [DISCIPLINAS Y OCUPACIONES] ,Bacteroides ,RNA in situ hybridization - Abstract
Simple Summary The analysis of colorectal cancer (CRC) gut microbiota can reveal crucial aspects of carcinogenesis and variation of treatment responses. Formalin-fixed, paraffin-embedded (FFPE) tissues represent an invaluable resource for studies in cancer genomics; however, their use in high-throughput metagenomic studies has been questioned due to several limitations in the DNA quality. In this study, we evaluated the impact of sample preservation on CRC-associated microbiota characterization. Using 16S rRNA sequencing and RNA in situ hybridization (RNA-ISH), we found differences in the comparison between paired FFPE and fresh frozen (FF) tissues, mostly derived from contamination issues. A quality index was also outlined to potentially assess the reliability of microbiome profiling obtained from FFPE DNA samples. These results suggest that tissular CRC microbiome studies should preserve internal coherence by using either FFPE or FF samples but not necessarily both. Abstract Formalin-fixed, paraffin-embedded (FFPE) tissues represent the most widely available clinical material to study colorectal cancer (CRC). However, the accuracy and clinical validity of FFPE microbiome profiling in CRC is uncertain. Here, we compared the microbial composition of 10 paired fresh-frozen (FF) and FFPE CRC tissues using 16S rRNA sequencing and RNA-ISH. Both sample types showed different microbial diversity and composition. FF samples were enriched in archaea and representative CRC-associated bacteria, such as Firmicutes, Bacteroidetes and Fusobacteria. Conversely, FFPE samples were mainly enriched in typical contaminants, such as Sphingomonadales and Rhodobacterales. RNA-ISH in FFPE tissues confirmed the presence of CRC-associated bacteria, such as Fusobacterium and Bacteroides, as well as Propionibacterium allowing discrimination between tumor-associated and contaminant taxa. An internal quality index showed that the degree of similarity within sample pairs inversely correlated with the dominance of contaminant taxa. Given the importance of FFPE specimens for larger studies in human cancer genomics, our findings may provide useful indications on potential confounding factors to consider for accurate and reproducible metagenomics analyses.
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- 2021
34. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses
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Jorge Carrillo, Joaquim Segalés, Mariona Parera, Tiziana Trogu, Santina Grazioli, Julià Blanco, Cristina Lorca-Oró, Nuria Izquierdo-Useros, Hugo Fernández-Bellon, Ana Moreno, Júlia Vergara-Alert, Pilar Padilla-Solé, Vanessa Almagro, Nuria Roca, Marc Noguera-Julian, Bonaventura Clotet, Rosa Valle, Leira Fernandez-Bastit, Albert Bensaid, Jordi Rodon, Producció Animal, and Sanitat Animal
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Lions ,Male ,viruses ,wildlife ,Animals, Wild ,Enzyme-Linked Immunosorbent Assay ,Genome, Viral ,Antibodies, Viral ,medicine.disease_cause ,Panthera leo ,Microbiology ,Article ,Animal Diseases ,zoo ,Virology ,biology.animal ,medicine ,Animals ,Respiratory system ,Feces ,Coronavirus ,lion ,CATS ,biology ,Transmission (medicine) ,SARS-CoV-2 ,COVID-19 ,Genomics ,Antibodies, Neutralizing ,QR1-502 ,Infectious Diseases ,Spain ,Infectious disease (medical specialty) ,Host-Pathogen Interactions ,biology.protein ,Animals, Zoo ,Female ,Panthera ,Antibody - Abstract
To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection. info:eu-repo/semantics/publishedVersion
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- 2021
35. Array-based Dynamic Allele Specific Hybridization (Array-DASH): optimization-free microarray processing for multiple simultaneous genomic assays
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Nathalie Zahra, Colin Veal, Caroline Howard, Maria Casadellà Fontdevila, Roger Paredes, Anthony J. Brookes, Spencer J. Gibson, Peter Freeman, Owen Lancaster, Marc Noguera-Julian, and Adrian Slater
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Genotyping ,HIV-1/genetics ,Microarray ,Coronavirus disease 2019 (COVID-19) ,Genotyping Techniques ,Computer science ,Biophysics ,Human immunodeficiency virus (HIV) ,Hybridization Array ,Computational biology ,Genome, Viral ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Genome ,Semi-quantitative ,03 medical and health sciences ,Hypericum/genetics ,medicine ,Humans ,Molecular Biology ,Allele specific ,030304 developmental biology ,COVID-19/epidemiology ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,010401 analytical chemistry ,COVID-19 ,HIV ,Cell Biology ,0104 chemical sciences ,HIV-1 ,Re-sequencing ,Hypericum ,Genome, Plant ,Software - Abstract
We report proof-of-principle experiments regarding a dynamic microarray protocol enabling accurate and semi-quantitative DNA analysis for re-sequencing, fingerprinting and genotyping. Single-stranded target molecules hybridise to surface-bound probes during initial gradual cooling with high-fidelity. Real-time tracking of target denaturation (via fluorescence) during a 'dynamic' gradual heating phase permits 'melt-curve' analysis. The probe most closely matching the target sequence is identified based on the highest melting temperature. We demonstrated a >99% re-sequencing accuracy and a potential detection rate of 1% for SNPs. Experiments employing Hypericum ribosomal ITS regions and HIV genomes illustrated a reliable detection level of 5% plus simultaneous re-sequencing and genotyping. Such performance suggests a range of potential real-world applications involving rapid sequence interrogation, for example, in the Covid-19 pandemic. Guidance is offered towards the development of a commercial platform and dedicated software required to bring this technique into mainstream science.
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- 2021
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36. SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells
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Jordana Muñoz-Basagoiti, Ferran Tarrés-Freixas, Benjamin Trinité, Martin Sachse, Sanjeev Gumber, Itziar Erkizia, Ester Ballana, Joaquim Segalés, Cristina Risco, Dàlia Raïch-Regué, Júlia Vergara-Alert, Maria Pino, Amalio Telenti, Nuria Izquierdo-Useros, Marc Elosua-Bayes, Jakub Chojnacki, Julià Blanco, Bonaventura Clotet, Victor Guallar, Roger Paredes, Jorge Carrillo, Mirko Paiardini, Ignacio Blanco, Daniel Perez-Zsolt, Holger Heyn, Xabier Muñiz-Trabudua, Marc Noguera-Julian, Javier Martinez-Picado, Eva Riveira-Muñoz, Jordi Rodon, Grifols, YoMeCorono, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, William I. H. and Lula E. Pitts Foundation, Ministerio de Economía y Competitividad (España), Rodón, Jordi [0000-0002-1032-9091], Raïch-Regué, Dàlia [0000-0001-7656-5700], Risco, Cristina [0000-0001-7501-5934], Paiardini, Mirko [0000-0002-7276-3600], Ballana, Ester [0000-0002-5215-7363], Carrillo, Jorge [0000-0003-0221-5948], Heyn, Holger [0000-0002-3276-1889], Segalés, Joaquim [0000-0002-1539-7261], Martínez-Picado, Javier [0000-0002-4916-2129], Izquierdo-Useros, Núria [0000-0002-1039-1821], Rodón, Jordi, Raïch-Regué, Dàlia, Risco, Cristina, Paiardini, Mirko, Ballana, Ester, Carrillo, Jorge, Heyn, Holger, Segalés, Joaquim, Martínez-Picado, Javier, and Izquierdo-Useros, Núria
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Sialic Acid Binding Ig-like Lectin 1 ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Trans infection ,Antigen-Presenting Cells ,Biology ,COVID-19 (Malaltia) ,Cell Line ,Correspondence ,Immunology and Allergy ,Humans ,skin and connective tissue diseases ,SARS-CoV-2 ,fungi ,SIGLEC ,COVID-19 ,Dendritic Cells ,respiratory system ,Virology ,N-Acetylneuraminic Acid ,body regions ,Infectious Diseases ,Mechanisms of disease ,Viral infection ,Genètica ,Receptors, Coronavirus - Abstract
Antigen-presenting cells (APCs) may be resistant to SARS-CoV-2 infection but still contribute to viral pathogenesis. Lectins such as sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) mediate the attachment of viruses to APCs. Here, we show that APCs effectively capture SARS-CoV-2 within compartments via recognition of Siglec-1. This receptor interacts with sialylated gangliosides on membranes of SARS-CoV-2 variants, as previously shown for retroviruses or filoviruses [1]. Blockage of Siglec-1 on monocyte-derived dendritic cells (MDDCs) decreased SARS-CoV-2 viral transfer or trans-infection to bystander target cells. However, monocyte-derived macrophages (MDMs) capturing SARS-CoV-2 via Siglec-1 did not transmit infectious particles. The presence of pulmonary APCs co-expressing Siglec-1 and SARS-CoV-2 corroborated these findings in vivo., The research of the CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols Pharmaceutical. The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N.I.-U. is supported by the grant PID2020-117145RB-I00 from the Spanish Ministry of Science and Innovation. J.M.-P. is supported by the grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part also by Grifols. The C.R. laboratory is funded by RTI2018-094445-B100 (MCIU/AEI/FEDER, UE). The NHP study was primarily supported by a YNPRC Coronavirus Pilot Research Project Program grant to M.Pa. under award P51 OD11132, Emergent Venture Fast grant program to M.Pa. under awards #2206 and #2144, and William and Lula Pitts Foundation (to M.Pa.). X.M.-T. is supported by the Spanish Ministry of Science and Innovation and the European Regional Development Fund under agreement BES-2017-082900.
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- 2021
37. Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in golden Syrian hamster
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Mónica Pérez, María Luisa Rodríguez de la Concepción, Jordi Rodon, Victor Guallar, Bonaventura Clotet, Marco Brustolin, Carlos Ávila-Nieto, Nuria Roca, Júlia Vergara-Alert, Albert Bensaid, Nuria Izquierdo-Useros, Guillermo Cantero, Jorge Carrillo, Nigeer Te, Marc Noguera-Julian, Alfonso Valencia, Joaquim Segalés, Julià Blanco, Barcelona Supercomputing Center, Producció Animal, and Sanitat Animal
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0301 basic medicine ,Male ,Epidemiology ,Coronaviruses ,golden Syrian hamster ,Golden Syrian hamster ,Antibodies, Viral ,Virus Replication ,COVID-19 (Malaltia) ,COVID-19 (Disease) ,Cricetinae ,Drug Discovery ,Protection ,Incidence (epidemiology) ,General Medicine ,Viral Load ,protection ,Immunohistochemistry ,Viral variants ,Animal models ,viral variants ,Infectious Diseases ,Host-Pathogen Interactions ,Female ,Infection ,Research Article ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,030106 microbiology ,Immunology ,Hamster ,Biology ,Re-infection ,Microbiology ,Cell Line ,03 medical and health sciences ,Animal model ,Neutralization Tests ,Virology ,medicine ,Animals ,Humans ,re-infection ,SARS-CoV-2 ,Public health ,animal model ,Immunity ,COVID-19 ,Antibodies, Neutralizing ,infection ,Immunity, Humoral ,Disease Models, Animal ,030104 developmental biology ,Reinfection ,Parasitology ,Immunological tolerance--Animal models ,Re infection - Abstract
Reinfections with SARS-CoV-2 have already been documented in humans, although its real incidence is currently unknown. Besides having a great impact on public health, this phenomenon raises the question of immunity generated by a single infection is sufficient to provide sterilizing/protective immunity to a subsequent SARS-CoV-2 re-exposure. The Golden Syrian hamster is a manageable animal model to explore immunological mechanisms able to counteract COVID-19, as it recapitulates pathological aspects of mild to moderately affected patients. Here, we report that SARS-CoV-2-inoculated hamsters resolve infection in the upper and lower respiratory tracts within seven days upon inoculation with the Cat01 (G614) SARS-CoV-2 isolate. Three weeks after the primary challenge, and despite high titres of neutralizing antibodies, half of the animals were susceptible to reinfection by both identical (Cat01, G614) and variant (WA/1, D614) SARS-CoV-2 isolates. However, upon re-inoculation, only nasal tissues were transiently infected with much lower viral replication than those observed after the first inoculation. These data indicate that a primary SARS-CoV-2 infection is not sufficient to elicit a sterilizing immunity in hamster models but protects against lung disease. The CBIG Consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. The authors also acknowledge the crowdfunding initiative of https://www.yomecorono.com. Peer Reviewed "Article signat per 19 autors/es: Marco Brustolin , Jordi Rodon , María Luisa Rodríguez de la Concepción , Carlos Ávila-Nieto , Guillermo Cantero , Mónica Pérez , Nigeer Te , Marc Noguera-Julián , Víctor Guallar , Alfonso Valencia, Núria Roca, Nuria Izquierdo-Useros, Julià Blanco, Bonaventura Clotet , Albert Bensaid , Jorge Carrillo , Júlia Vergara-Alert , Joaquim Segalés "
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- 2021
38. Dry Panels Supporting External Quality Assessment Programs for Next Generation Sequencing-Based HIV Drug Resistance Testing
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Emma R. Lee, Hezhao Ji, Robert W. Shafer, Rami Kantor, and Marc Noguera-Julian
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0301 basic medicine ,Computer science ,Human immunodeficiency virus (HIV) ,lcsh:QR1-502 ,HIV Infections ,Microbial Sensitivity Tests ,medicine.disease_cause ,Bottleneck ,DNA sequencing ,lcsh:Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Software ,Clinical report ,Virology ,Drug Resistance, Viral ,External quality assessment ,medicine ,Humans ,030212 general & internal medicine ,dry panel ,next generation sequencing ,Sequence Analysis, RNA ,business.industry ,Computational Biology ,High-Throughput Nucleotide Sequencing ,HIV ,external quality assessment ,Data science ,030104 developmental biology ,Infectious Diseases ,Commentary ,HIV-1 ,business ,drug resistance testing ,HIV drug resistance - Abstract
External quality assessment (EQA) is a keystone element in the validation and implementation of next generation sequencing (NGS)-based HIV drug resistance testing (DRT). Software validation and evaluation is a critical element in NGS EQA programs. While the development, sharing, and adoption of wet lab protocols is coupled with the increasing access to NGS technology worldwide, rendering it easy to produce NGS data for HIV-DRT, bioinformatic data analysis remains a bottleneck for most of the diagnostic laboratories. Several computational tools have been made available, via free or commercial sources, to automate the conversion of raw NGS data into an actionable clinical report. Although different software platforms yield equivalent results when identical raw NGS datasets are analyzed for variations at higher abundance, discrepancies arise when variations at lower frequencies are considered. This implies that validation and performance assessment of the bioinformatics tools applied in NGS HIV-DRT is critical, and the origins of the observed discrepancies should be determined. Well-characterized reference NGS datasets with ground truth on the genotype composition at all examined loci and the exact frequencies of HIV variations they may harbor, so-called dry panels, would be essential in such cases. The strategic design and construction of such panels are challenging but imperative tasks in support of EQA programs for NGS-based HIV-DRT and the validation of relevant bioinformatics tools. Here, we present criteria that can guide the design of such dry panels, which were discussed in the Second International Winnipeg Symposium themed for EQA strategies for NGS HIVDR assays.
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- 2020
39. Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain
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Mariona Parera, Carlos Ávila-Nieto, Júlia Vergara-Alert, Joaquim Segalés, Jordi Rodon, Maria Teresa Terrón, Ignacio Blanco, Sílvia Cruz, Victor Guallar, Julià Blanco, Alfonso Valencia, Jorge Carrillo, Bonaventura Clotet, Mariona Puig, Marc Noguera-Julian, Nuria Izquierdo-Useros, Guillermo Cantero, Enric Vidal, Producció Animal, Sanitat Animal, and Barcelona Supercomputing Center
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0301 basic medicine ,040301 veterinary sciences ,viruses ,Pneumonia, Viral ,Cardiomyopathy ,cat ,Disease ,COVID-19 (Malaltia) ,0403 veterinary science ,03 medical and health sciences ,Betacoronavirus ,Fatal Outcome ,COVID-19 (Disease) ,Medicine ,Animals ,Humans ,Transmission ,Pandemics ,Subclinical infection ,Incidental Findings ,Multidisciplinary ,Respiratory distress ,business.industry ,Transmission (medicine) ,Agricultural Sciences ,SARS-CoV-2 ,transmission ,COVID-19 ,Cat ,04 agricultural and veterinary sciences ,Biological Sciences ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Pulmonary edema ,030104 developmental biology ,Nasal Swab ,Immunology ,Etiology ,Cats ,business ,Coronavirus Infections ,Ciències de la salut [Àrees temàtiques de la UPC] - Abstract
Significance COVID-19 is the most devastating pandemic in recent history. As with many emerging infectious diseases, it is of zoonotic origin, meaning that animals played a major role in the initial transmission events. Despite SARS-CoV-2 being highly adapted to jump from human to human, several animal species are naturally susceptible to SARS-CoV-2, including pets such as cats. In the present report, a cat from a family with several relatives affected by COVID-19 developed severe respiratory clinical signs, leading to humanitarian euthanasia. Due to the suspicion of a potential COVID-19 infection in the cat, different antemortem and postmortem tests were assayed. The clinical condition was finally attributed to a feline hypertrophic cardiomyopathy, but the animal was also infected by SARS-CoV-2., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19−like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia.
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- 2020
40. Associations of the gut microbiome and clinical factors with acute GVHD in allogeneic HSCT recipients
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Daniel D Murray, Gedske Daugaard, Mette Jørgensen, Joanne Reekie, Roger Paredes, Cameron Ross MacPherson, Jens Christian Nørgaard, Henrik Sengeløv, Jens D Lundgren, Emma E Ilett, Marie Helleberg, and Marc Noguera-Julian
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0301 basic medicine ,Adult ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Disease ,Hematopoietic stem cell transplantation ,Biology ,Gut flora ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,RNA, Ribosomal, 16S ,medicine ,Humans ,Transplantation ,Hematopoietic Stem Cell Transplantation ,Hematology ,biology.organism_classification ,Gut microbiome ,Gastrointestinal Microbiome ,030104 developmental biology ,Enterococcus ,030220 oncology & carcinogenesis ,Allogeneic hsct ,Immunology ,Akkermansia muciniphila - Abstract
Acute graft-versus-host disease (aGVHD) is a leading cause of transplantation-related mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). 16S ribosomal RNA (16S rRNA) gene-based studies have reported that lower gut bacterial diversity and the relative abundance of certain bacteria after aHSCT are associated with aGVHD. Using shotgun metagenomic sequencing and a large cohort, we aimed to confirm and extend these observations. Adult aHSCT recipients with stool samples collected from day −30 to day 100 relative to aHSCT were included. One sample was selected per patient per period (pre-aHSCT (day −30 to day 0), early post-aHSCT (day 1 to day 28), and late post-aHSCT (day 29 to day 100)), resulting in 150 aHSCT recipients and 259 samples. Microbial and clinical factors were tested for differences between time periods and an association with subsequent aGVHD. Patients showed a decline in gut bacterial diversity posttransplant, with several patients developing a dominance of Enterococcus. A total of 36 recipients developed aGVHD at a median of 34 days (interquartile range, 26-50 days) post-aHSCT. Lower microbial gene richness (P = .02), a lower abundance of the genus Blautia (P = .05), and a lower abundance of Akkermansia muciniphila (P = .01) early post-aHSCT was observed in those who developed aGVHD. Myeloablative conditioning was associated with aGVHD along with a reduction in gene richness and abundance of Blautia and A muciniphila. These results confirm low diversity and Blautia being associated with aGVHD. Crucially, we add that pretransplant conditioning is associated with changes in gut microbiota. Investigations are warranted to determine the interplay of gut microbiota and conditioning in the development of aGVHD.
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- 2020
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41. Are We Ready for NGS HIV Drug Resistance Testing? The Second 'Winnipeg Consensus' Symposium
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P. Richard Harrigan, Chanson J. Brumme, Paul Sandstrom, Hezhao Ji, Santiago Avila Rios, Marc Noguera-Julian, Rami Kantor, Roger Paredes, and Neil Parkin
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0301 basic medicine ,Winnipeg Consensus ,medicine.medical_specialty ,Anti-HIV Agents ,030106 microbiology ,lcsh:QR1-502 ,HIV Infections ,lcsh:Microbiology ,03 medical and health sciences ,Virology ,Political science ,Drug Resistance, Viral ,medicine ,Humans ,Clinical care ,symposium ,Public health ,HIV ,High-Throughput Nucleotide Sequencing ,Congresses as Topic ,Antiretroviral therapy ,030104 developmental biology ,Infectious Diseases ,Family medicine ,NGS ,Commentary ,HIV drug resistance testing ,HIV drug resistance - Abstract
HIV drug resistance is a major global challenge to successful and sustainable antiretroviral therapy. Next-generation sequencing (NGS)-based HIV drug resistance (HIVDR) assays enable more sensitive and quantitative detection of drug-resistance-associated mutations (DRMs) and outperform Sanger sequencing approaches in detecting lower abundance resistance mutations. While NGS is likely to become the new standard for routine HIVDR testing, many technical and knowledge gaps remain to be resolved before its generalized adoption in regular clinical care, public health, and research. Recognizing this, we conceived and launched an international symposium series on NGS HIVDR, to bring together leading experts in the field to address these issues through in-depth discussions and brainstorming. Following the first symposium in 2018 (Winnipeg, MB Canada, 21–22 February, 2018), a second “Winnipeg Consensus” symposium was held in September 2019 in Winnipeg, Canada, and was focused on external quality assurance strategies for NGS HIVDR assays. In this paper, we summarize this second symposium’s goals and highlights.
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- 2020
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42. Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study
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Jordi Navarro, Beatriz Mothe, Christian Brander, Roger Paredes, Javier Rivera, Bonaventura Clotet, M. L. Calle, Mariona Parera, Muntsa Rocafort, Manel Crespo, Marc Noguera-Julian, Eugenia Negredo, J Saz, Yolanda Guillén, Josep Coll, and Maria Casadellà
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Genetics ,Microarray ,Host (biology) ,Genomics ,Enterotype ,Microbiome ,Biology ,Gut flora ,biology.organism_classification ,Gene ,Exome - Abstract
The impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the host’s genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.
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- 2018
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43. Balances: a New Perspective for Microbiome Analysis
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M. Luz Calle, Javier Rivera Pinto, Marc Noguera-Julian, Roger Paredes, Juan José Egozcue, Vera Pawlowsky-Glahn, Universitat Politècnica de Catalunya. Departament d'Enginyeria Civil i Ambiental, and Universitat Politècnica de Catalunya. COSDA-UPC - COmpositional and Spatial Data Analysis
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0301 basic medicine ,Ciències de la salut::Medicina [Àrees temàtiques de la UPC] ,Physiology ,Absolute quantification ,030106 microbiology ,Human immunodeficiency virus (HIV) ,lcsh:QR1-502 ,Matemàtiques i estadística::Matemàtica aplicada a les ciències [Àrees temàtiques de la UPC] ,microbiome ,Microorganismes ,Computational biology ,Compositional data ,Biology ,medicine.disease_cause ,Biochemistry ,Microbiology ,lcsh:Microbiology ,Host-Microbe Biology ,Balances ,03 medical and health sciences ,Abundance (ecology) ,balances ,Genetics ,medicine ,Microbiome ,Molecular Biology ,Relative species abundance ,Ecology, Evolution, Behavior and Systematics ,Selection (genetic algorithm) ,Ecology ,Microbiota ,Methods and Protocols ,Univariate ,food and beverages ,QR1-502 ,Computer Science Applications ,compositional data ,030104 developmental biology ,Taxon ,Evolutionary biology ,Modeling and Simulation ,Identification (biology) ,Balance of nature - Abstract
We propose a new algorithm for the identification of microbial signatures. These microbial signatures can be used for diagnosis, prognosis, or prediction of therapeutic response based on an individual’s specific microbiota., High-throughput sequencing technologies have revolutionized microbiome research by allowing the relative quantification of microbiome composition and function in different environments. In this work we focus on the identification of microbial signatures, groups of microbial taxa that are predictive of a phenotype of interest. We do this by acknowledging the compositional nature of the microbiome and the fact that it carries relative information. Thus, instead of defining a microbial signature as a linear combination in real space corresponding to the abundances of a group of taxa, we consider microbial signatures given by the geometric means of data from two groups of taxa whose relative abundances, or balance, are associated with the response variable of interest. In this work we present selbal, a greedy stepwise algorithm for selection of balances or microbial signatures that preserves the principles of compositional data analysis. We illustrate the algorithm with 16S rRNA abundance data from a Crohn’s microbiome study and an HIV microbiome study. IMPORTANCE We propose a new algorithm for the identification of microbial signatures. These microbial signatures can be used for diagnosis, prognosis, or prediction of therapeutic response based on an individual’s specific microbiota.
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- 2018
44. Primary resistance to integrase strand transfer inhibitors in patients infected with diverse HIV-1 subtypes in sub-Saharan Africa
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Tobias F. Rinke de Wit, Mariona Parera, Raph L. Hamers, Marc Noguera-Julian, Roger Paredes, Seth C Inzaule, Maria Casadellà, APH - Quality of Care, APH - Personalized Medicine, Graduate School, Other departments, and Global Health
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,Sub saharan ,Genotype ,030106 microbiology ,Mutation, Missense ,HIV Infections ,Drug resistance ,HIV Integrase ,medicine.disease_cause ,Strand transfer ,03 medical and health sciences ,symbols.namesake ,Gene Frequency ,Drug Resistance, Viral ,medicine ,Prevalence ,Humans ,Pharmacology (medical) ,In patient ,HIV Integrase Inhibitors ,Africa South of the Sahara ,Pharmacology ,Sanger sequencing ,Mutation ,biology ,High-Throughput Nucleotide Sequencing ,Virology ,Integrase ,Infectious Diseases ,Case-Control Studies ,symbols ,biology.protein ,HIV-1 ,Female - Abstract
Objectives To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa. Methods pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%–20% for low-frequency variants (next-generation sequencing). Results Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at Conclusions Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region.
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- 2018
45. Clinically relevant thresholds for ultrasensitive HIV drug resistance testing: a multi-country nested case-control study
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Sulaimon Akanmu, Akin Osibogun, Jack Menke, Titilope A Adeyemo, Miiro Mutebi, Ian Sanne, Cissy Kityo, Kim C. E. Sigaloff, Seth C Inzaule, Esrom Letsoalo, Miriam Nakitto, Margaret Siwale, Tope Rodoye, Cathy Nalubwama, H. Namata, Denise Naniche, Ritah Nakanjako, Mariette E. Botes, Pascale Ondoa, Wendy S. Stevens, Martin O'Mello, Ruedi Lüthy, Carole L. Wallis, Fred Senono, Marian Dolan, Hameed Adelabu, Immaculate Nankya, Mariona Parera, Hanipha Kakooza, Maria Casadellà, T. Sonia Boender, Roger Paredes, Raph L. Hamers, Margaret Hardman, Kishor Mandaliya, Tobias F. Rinke de Wit, Marc Noguera-Julian, Joep M. A. Lange, Marleen de Jager, Maureen Wellington, Kim Steegen, Nadine Pakker, Sheila Balinda, Bonaventura Clotet, Moheb Labib, Rob Schuurman, Prudence Ive, Winnie Namala, Peter Mugyenyi, Global Health, Graduate School, AII - Infectious diseases, APH - Personalized Medicine, APH - Quality of Care, APH - Methodology, and Intensive care medicine
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Genotype ,Epidemiology ,Anti-HIV Agents ,Immunology ,HIV Infections ,Drug resistance ,Sensitivity and Specificity ,03 medical and health sciences ,Virology ,Internal medicine ,Drug Resistance, Viral ,medicine ,Odds Ratio ,media_common.cataloged_instance ,Humans ,Prospective Studies ,Treatment Failure ,European union ,Prospective cohort study ,Africa South of the Sahara ,media_common ,business.industry ,Odds ratio ,Viral Load ,CD4 Lymphocyte Count ,Regimen ,030104 developmental biology ,Infectious Diseases ,Case-Control Studies ,Nested case-control study ,HIV-1 ,RNA, Viral ,Reverse Transcriptase Inhibitors ,Female ,business ,Viral load ,HIV drug resistance - Abstract
BACKGROUND: Implementation of ultrasensitive HIV drug resistance tests for routine clinical use is hampered by uncertainty about the clinical relevance of drug-resistant minority variants. We assessed different detection thresholds for pretreatment drug resistance to predict an increased risk of virological failure.METHODS: We did a case-control study nested within a prospective multicountry cohort. Our study included patients from 12 clinical sites in Kenya, Nigeria, South Africa, Uganda, and Zambia. We defined cases as patients with virological failure (ie, those who had either viral load ≥400 copies per mL at 12 months or had switched to second-line antiretroviral therapy [ART] as a result of virological failure before 12 months) and controls as those with viral suppression (viral load FINDINGS: Paired viral load results before ART and at month 12 of follow-up were available from 1896 participants. We identified 178 patients with virological failure and selected 338 matched controls. We excluded 117 patients from pretreatment drug resistance analysis; therefore, 152 cases of virological failure and 247 controls were included in the final analysis. With the IAS-USA mutation list, at a detection threshold of 20% or more in patients with pretreatment drug resistance, the adjusted odds ratio (OR) for virological failure was 9·2 (95% CI 4·2-20·1) compared with those without pretreatment drug resistance. Lowering the threshold resulted in adjusted ORs of virological failure of 6·8 (95% CI 3·3-13·9) at the 10% threshold, 7·6 (3·4-17·1) at the 5% threshold, and 4·5 (2·0-10·2) at the 1% threshold. Lowering the detection threshold from 20% improved the sensitivity (ie, ability to identify cases) from 12% (n=18) to 13% (n=19) at detection threshold 10%, to 15% (n=23) at detection threshold 5%, and to 17% (n=26) at detection threshold 1%, but caused a slight reduction in specificity (ie, ability to identify controls) from 98% (n=241) to 96% (n=238) at the 10% threshold, 96% (n=236) at the 5% threshold, and a larger reduction to 92% (n=227) at the 1% threshold. Diagnostic ORs were 5·4 (95% CI 2·1-13·9) at the 20% threshold, 3·8 (1·7-8·6) at the 10% threshold, 3·8 (1·8-8·1) at the 5% threshold, and 2·3 (1·2-4·2) at the 1% threshold. Use of the Stanford HIVDB genotypic sensitivity scores yielded similar ORs for virological failure, sensitivities, specificities, and diagnostic ORs.INTERPRETATION: Ultrasensitive resistance testing for pretreatment drug resistance improved identification of people at risk of virological failure; however, this came with a reduction in our ability to identify people with viral suppression, especially at very low thresholds. Further modelling is needed to estimate the optimal trade-off for the 5% and 20% thresholds, balancing improved case finding against unnecessary regimen switching.FUNDING: The Netherlands Ministry of Foreign Affairs, IrsiCaixa, and European Union.
- Published
- 2018
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46. Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B
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Christian Brander, Marc Noguera-Julian, Jose L. Jimenez, Julià Blanco, Rocío Bellido, Jorge Carrillo, Miriam Rosás-Umbert, Mariano Esteban, Felipe García, Patricia Cobarsi, Beatriz Mothe, Roger Paredes, Carmen E. Gómez, Carmen Rodríguez, Maria C. Puertas, Javier Martinez-Picado, and Núria Pérez-Álvarez
- Subjects
0301 basic medicine ,RNA viruses ,Cellular immunity ,Viral Diseases ,Immunogen ,lcsh:Medicine ,HIV Infections ,Pathology and Laboratory Medicine ,White Blood Cells ,Immunodeficiency Viruses ,Animal Cells ,Medicine and Health Sciences ,Public and Occupational Health ,lcsh:Science ,Immune Response ,AIDS Vaccines ,education.field_of_study ,Vaccines ,Multidisciplinary ,T Cells ,MVA-B ,Vaccination ,virus diseases ,Viral Load ,Vaccination and Immunization ,Treatment Outcome ,Infectious Diseases ,Cèl·lules T ,Medical Microbiology ,Viral Pathogens ,Viruses ,Cellular Types ,Pathogens ,Research Article ,HIV infections ,Infectious Disease Control ,Immune Cells ,Population ,Immunology ,T cells ,Viremia ,Human leukocyte antigen ,Microbiology ,Virus ,03 medical and health sciences ,Vacunes antivíriques ,Virology ,Retroviruses ,medicine ,Humans ,education ,Microbial Pathogens ,Blood Cells ,business.industry ,Viral vaccines ,lcsh:R ,Lentivirus ,Organisms ,Biology and Life Sciences ,HIV ,Viral Vaccines ,Cell Biology ,medicine.disease ,Immunity, Humoral ,030104 developmental biology ,DNA, Viral ,HIV-1 ,lcsh:Q ,Infeccions per VIH ,Preventive Medicine ,business ,Viral Transmission and Infection - Abstract
The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches.
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- 2017
47. Next-Generation Human Immunodeficiency Virus Sequencing for Patient Management and Drug Resistance Surveillance
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Paul Sandstrom, Catherine Godfrey, Roger Paredes, Dianna Edgil, P. Richard Harrigan, and Marc Noguera-Julian
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0301 basic medicine ,medicine.medical_specialty ,Computer science ,Anti-HIV Agents ,Population ,Human immunodeficiency virus (HIV) ,Supplement Articles ,HIV Infections ,Drug resistance ,medicine.disease_cause ,03 medical and health sciences ,symbols.namesake ,Health care ,Drug Resistance, Viral ,medicine ,Immunology and Allergy ,Humans ,education ,Hiv resistance ,Sanger sequencing ,education.field_of_study ,business.industry ,Public health ,public health ,HIV resistance ,HIV ,High-Throughput Nucleotide Sequencing ,bioinformatics ,Cloud Computing ,Data science ,Virology ,Patient management ,030104 developmental biology ,Infectious Diseases ,NGS ,surveillance ,symbols ,business - Abstract
High-quality, simplified, and low-cost human immunodeficiency virus (HIV) drug resistance tests that are able to provide timely actionable HIV resistance data at individual, population, and programmatic levels are needed to confront the emerging drug-resistant HIV epidemic. Next-generation sequencing technologies embedded in automated cloud-computing analysis environments are ideally suited for such endeavor. Whereas NGS can reduce costs over Sanger sequencing, automated analysis pipelines make NGS accessible to molecular laboratories regardless of the available bioinformatic skills. They can also produce highly structured, high-quality data that could be examined by healthcare officials and program managers on a real-time basis to allow timely public health action. Here we discuss the opportunities and challenges of such an approach.
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- 2017
48. Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART
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Gerardo del Carmen Palacios-Saucedo, Jorge García-Campos, Marcelino Chavez-García, Roger Paredes, Lydia G. Rivera-Morales, Carlos Alberto Vázquez-Martínez, Evangelina Briones-Lara, Herlinda J. Vielma-Ramirez, Rocio Ortiz-Lopez, Marc Noguera-Julian, Cristina Rodríguez-Padilla, Luz María Sánchez-Sánchez, Jose Manuel Vazquez-Guillen, Paulo Lopez-Guillen, and T. Ramirez
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RNA viruses ,Male ,0301 basic medicine ,Gene Identification and Analysis ,Human immunodeficiency virus (HIV) ,lcsh:Medicine ,HIV Infections ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Pediatrics ,Biochemistry ,Antiretroviral resistance ,Immunodeficiency Viruses ,Antiretroviral Therapy, Highly Active ,Genotype ,Medicine and Health Sciences ,Medicine ,Public and Occupational Health ,lcsh:Science ,Multidisciplinary ,Antimicrobials ,Microbial Mutation ,Sida Tractament ,Drugs ,Antiretrovirals ,High-Throughput Nucleotide Sequencing ,Proteases ,Viral Load ,Antivirals ,Vaccination and Immunization ,Enzymes ,Medical Microbiology ,Viral Pathogens ,Viruses ,Female ,Pathogens ,Pediatric Infections ,Viral load ,Structured Treatment Interruptions (STI) ,Research Article ,Adolescent ,Anti-HIV Agents ,Immunology ,Antiretroviral Therapy ,Viral quasispecies ,Microbiology ,03 medical and health sciences ,Antiviral Therapy ,Microbial Control ,Virology ,Retroviruses ,Drug Resistance, Viral ,Genetics ,Highly-Active Antiretroviral Therapy ,Humans ,Mutation Detection ,Microbial Pathogens ,Genotyping ,Pharmacology ,business.industry ,Lentivirus ,lcsh:R ,Organisms ,Biology and Life Sciences ,HIV ,Proteins ,Ultra deep sequencing ,VIH (Virus) Tractament ,Reverse transcriptase ,VIROLOGIC FAILURE ,030104 developmental biology ,Mutation ,HIV-1 ,Enzymology ,lcsh:Q ,Preventive Medicine ,Structured interruptions of HAART ,business - Abstract
Altres ajuts: CONACYT/GCPS/44519 Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (
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- 2016
49. Decreased phenotypic susceptibility to etravirine in patients with predicted genotypic sensitivity
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Anders Sönnerborg, Piotr Nowak, Roger Paredes, Maria Casadellà, Catharina Maijgren Steffensson, Marc Noguera-Julian, Clas Källander, and Eva Agneskog
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Adult ,Male ,Viral Diseases ,Genotype ,Anti-HIV Agents ,DNA Mutational Analysis ,Sexually Transmitted Diseases ,Etravirine ,lcsh:Medicine ,Drug resistance ,Biology ,Microbiology ,Virus ,Inhibitory Concentration 50 ,Immunodeficiency Viruses ,Virology ,Drug Resistance, Viral ,Nitriles ,medicine ,Humans ,Clinical significance ,lcsh:Science ,Microbial Pathogens ,Medicine and health sciences ,Multidisciplinary ,Reverse-transcriptase inhibitor ,lcsh:R ,Biology and Life Sciences ,HIV ,HIV diagnosis and management ,Middle Aged ,Reverse transcriptase ,HIV Reverse Transcriptase ,Diagnostic medicine ,Pyridazines ,Phenotype ,Pyrimidines ,Infectious Diseases ,Medical Microbiology ,Viral Pathogens ,HIV-1 ,Pyrosequencing ,Reverse Transcriptase Inhibitors ,Female ,lcsh:Q ,medicine.drug ,Research Article - Abstract
BACKGROUND: A sensitive, phenotypic reverse transcriptase (RT)-based drug susceptibility assay for the detection of etravirine (ETR) resistance in patient isolates was developed and compared with the results from direct sequencing and ultra-deep pyrosequencing (UDPS). METHODS: Samples were obtained from 15 patients with antiretroviral therapy (ART) failure and from five non-nucleoside reverse transcriptase inhibitor (NNRTI)-naïve patients of whom four were infected by an NNRTI-resistant strain (transmitted drug resistance, TDR). In five patients, two consecutive samples (a and b) were taken for follow up of the virological response. HIV-1 RT was purified and drug susceptibility (IC50) to ETR was estimated. Direct sequencing was performed in all samples and UDPS in samples from nine patients. RESULTS: Increased IC50 to ETR was found in samples from 13 patients where direct sequencing predicted resistance in only four. UDPS identified additional (N = 11) NNRTI resistance associated mutations (RAMs) in six of nine tested patients. During early failure, IC50 increases were observed in three of six patients without any ETR-RAMs detected by direct sequencing. In further two patients, who stopped NNRTI before sampling, increased IC50 values were found shortly after, despite absence of ETR-RAMs. In two patients who had stopped NNRTI for >1 year, a concordance between phenotype and genotypes was found. Two patients with TDR had increased IC50 despite no ETR-RAMs were detected by direct sequencing. UDPS revealed additional ETR-RAMs in four patients with a discrepancy between phenotype and direct sequencing. CONCLUSIONS: The RT-based phenotypic assay showed decreased ETR susceptibility in patients where direct sequencing predicted ETR-sensitive virus. This increased phenotypic sensitivity was to a large extent supported by UDPS and treatment history. Our method could be valuable for further studies on the phenotypic kinetics of NNRTI resistance. The clinical relevance remains to be studied in larger patient-populations.
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- 2014
50. HIV-1 Tropism Testing in Subjects Achieving Undetectable HIV-1 RNA: Diagnostic Accuracy, Viral Evolution and Compartmentalization
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Marta Curriu, Judith Dalmau, Alexander Thielen, Bonaventura Clotet, Roger Paredes, Martin Daumer, Rocío Bellido, Francisco M. Codoñer, Javier Martinez-Picado, Susana Pérez-Álvarez, Yolanda Lie, Cecilia Cabrera, Julià Blanco, Marc Noguera-Julian, Christian Pou, Jordi Puig, and Eoin Coakley
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Male ,Time Factors ,viruses ,lcsh:Medicine ,HIV Infections ,HIV Envelope Protein gp120 ,Hiv 1 rna ,Blood plasma ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,virus diseases ,HIV diagnosis and management ,Hematology ,Compartmentalization (psychology) ,Middle Aged ,3. Good health ,Phenotype ,Viral evolution ,Medicine ,Infectious diseases ,RNA, Viral ,Female ,Research Article ,Test Evaluation ,Adult ,Receptors, CXCR4 ,Genotype ,Molecular Sequence Data ,Retrovirology and HIV immunopathogenesis ,Viremia ,Viral diseases ,Biology ,Peripheral blood mononuclear cell ,Microbiology ,Sensitivity and Specificity ,Viral Evolution ,Evolution, Molecular ,03 medical and health sciences ,Diagnostic Medicine ,Virology ,medicine ,Humans ,Amino Acid Sequence ,Tropism ,030304 developmental biology ,Retrospective Studies ,030306 microbiology ,lcsh:R ,HIV ,medicine.disease ,Peptide Fragments ,Viral Disease Diagnosis ,Viral Tropism ,Tissue tropism ,HIV-1 ,lcsh:Q - Abstract
BACKGROUND: Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. METHODS & RESULTS: We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA
- Published
- 2013
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