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1. A graph neural network-based model with Out-of-Distribution Robustness for enhancing Antiretroviral Therapy Outcome Prediction for HIV-1

Author

Di Teodoro, Giulia, Siciliano, Federico, Guarrasi, Valerio, Vandamme, Anne-Mieke, Ghisetti, Valeria, Sönnerborg, Anders, Zazzi, Maurizio, Silvestri, Fabrizio, and Palagi, Laura

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Machine Learning, 68, I.2.6
Abstract

Predicting the outcome of antiretroviral therapies for HIV-1 is a pressing clinical challenge, especially when the treatment regimen includes drugs for which limited effectiveness data is available. This scarcity of data can arise either due to the introduction of a new drug to the market or due to limited use in clinical settings. To tackle this issue, we introduce a novel joint fusion model, which combines features from a Fully Connected (FC) Neural Network and a Graph Neural Network (GNN). The FC network employs tabular data with a feature vector made up of viral mutations identified in the most recent genotypic resistance test, along with the drugs used in therapy. Conversely, the GNN leverages knowledge derived from Stanford drug-resistance mutation tables, which serve as benchmark references for deducing in-vivo treatment efficacy based on the viral genetic sequence, to build informative graphs. We evaluated these models' robustness against Out-of-Distribution drugs in the test set, with a specific focus on the GNN's role in handling such scenarios. Our comprehensive analysis demonstrates that the proposed model consistently outperforms the FC model, especially when considering Out-of-Distribution drugs. These results underscore the advantage of integrating Stanford scores in the model, thereby enhancing its generalizability and robustness, but also extending its utility in real-world applications with limited data availability. This research highlights the potential of our approach to inform antiretroviral therapy outcome prediction and contribute to more informed clinical decisions., Comment: 32 pages, 2 figures

Published
2023

2. Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1

Author

Di Teodoro, Giulia, Pirkl, Martin, Incardona, Francesca, Vicenti, Ilaria, Sönnerborg, Anders, Kaiser, Rolf, Palagi, Laura, Zazzi, Maurizio, and Lengauer, Thomas

Subjects
Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods
Abstract

Motivation: In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using it (NH). Results: The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Significant Wilcoxon test results confirm that incorporating historical information improves consistently predictive accuracy for treatment outcomes. The better performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in mutations, offering insights into HIV infection complexities. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. Supplementary information: Supplementary material is available., Comment: 16 pages, 6 figures

Published
2023
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4. Generating Synthetic Clinical Data that Capture Class Imbalanced Distributions with Generative Adversarial Networks: Example using Antiretroviral Therapy for HIV

Author

Kuo, Nicholas I-Hsien, Garcia, Federico, Sönnerborg, Anders, Zazzi, Maurizio, Böhm, Michael, Kaiser, Rolf, Polizzotto, Mark, Jorm, Louisa, and Barbieri, Sebastiano

Subjects
Computer Science - Machine Learning
Abstract

Clinical data usually cannot be freely distributed due to their highly confidential nature and this hampers the development of machine learning in the healthcare domain. One way to mitigate this problem is by generating realistic synthetic datasets using generative adversarial networks (GANs). However, GANs are known to suffer from mode collapse thus creating outputs of low diversity. This lowers the quality of the synthetic healthcare data, and may cause it to omit patients of minority demographics or neglect less common clinical practices. In this paper, we extend the classic GAN setup with an additional variational autoencoder (VAE) and include an external memory to replay latent features observed from the real samples to the GAN generator. Using antiretroviral therapy for human immunodeficiency virus (ART for HIV) as a case study, we show that our extended setup overcomes mode collapse and generates a synthetic dataset that accurately describes severely imbalanced class distributions commonly found in real-world clinical variables. In addition, we demonstrate that our synthetic dataset is associated with a very low patient disclosure risk, and that it retains a high level of utility from the ground truth dataset to support the development of downstream machine learning algorithms., Comment: In the near future, we will make our codes and synthetic datasets publicly available to facilitate future research. Follow us on https://healthgym.ai/

Published
2022

5. The Health Gym: Synthetic Health-Related Datasets for the Development of Reinforcement Learning Algorithms

Author

Kuo, Nicholas I-Hsien, Polizzotto, Mark N., Finfer, Simon, Garcia, Federico, Sönnerborg, Anders, Zazzi, Maurizio, Böhm, Michael, Jorm, Louisa, and Barbieri, Sebastiano

Subjects
Computer Science - Machine Learning
Abstract

In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their highly confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care. Here we introduce the Health Gym - a growing collection of highly realistic synthetic medical datasets that can be freely accessed to prototype, evaluate, and compare machine learning algorithms, with a specific focus on reinforcement learning. The three synthetic datasets described in this paper present patient cohorts with acute hypotension and sepsis in the intensive care unit, and people with human immunodeficiency virus (HIV) receiving antiretroviral therapy in ambulatory care. The datasets were created using a novel generative adversarial network (GAN). The distributions of variables, and correlations between variables and trends over time in the synthetic datasets mirror those in the real datasets. Furthermore, the risk of sensitive information disclosure associated with the public distribution of the synthetic datasets is estimated to be very low.

Published
2022

7. EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project

Author

Hedberg, Pontus, Varisco, Benedetta, Bai, Francesca, Sönnerborg, Anders, Naucler, Pontus, Pfeifer, Nico, Cozzi-Lepri, Alessandro, Ceccherini-Silberstein, Francesca, Naumovas, Daniel, Drobniewski, Francis, Jensen, Björn-Erik Ole, Toscano, Cristina, Parczewski, Miłosz, Quintanares, Gibran Horemheb Rubio, Mwau, Matilu, Pinto, Jorge A., Incardona, Francesca, Mommo, Chiara, and Marchetti, Giulia

Published
2023
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8. In-hospital mortality during the wild-type, alpha, delta, and omicron SARS-CoV-2 waves: a multinational cohort study in the EuCARE project

Author

Hedberg, Pontus, Parczewski, Milosz, Serwin, Karol, Marchetti, Giulia, Bai, Francesca, Ole Jensen, Björn-Erik, Pereira, Joana P.V., Drobniewski, Francis, Reschreiter, Henrik, Naumovas, Daniel, Ceccherini-Silberstein, Francesca, Rubio Quintanares, Gibran Horemheb, Mwau, Matilu, Toscano, Cristina, König, Florian, Pfeifer, Nico, Zazzi, Maurizio, Fanti, Iuri, Incardona, Francesca, Cozzi-Lepri, Alessandro, Sönnerborg, Anders, and Nauclér, Pontus

Published
2024
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10. High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

Author

Karolinska KI/K COVID-19 Study Group, Lourda, Magda, Dzidic, Majda, Hertwig, Laura, Bergsten, Helena, Medina, Laura M. Palma, Sinha, Indranil, Kvedaraite, Egle, Chen, Puran, Muvva, Jagadeeswara R., Gorin, Jean-Baptiste, Cornillet, Martin, Emgård, Johanna, Moll, Kirsten, García, Marina, Maleki, Kimia T., Klingström, Jonas, Michaëlsson, Jakob, Flodström-Tullberg, Malin, Brighenti, Susanna, Buggert, Marcus, Mjösberg, Jenny, Malmberg, Karl-Johan, Sandberg, Johan K., Henter, Jan-Inge, Folkesson, Elin, Gredmark-Russ, Sara, Sönnerborg, Anders, Eriksson, Lars I., Rooyackers, Olav, Aleman, Soo, Strålin, Kristoffer, Ljunggren, Hans-Gustaf, Björkström, Niklas K., Svensson, Mattias, Ponzetta, Andrea, Norrby-Teglund, Anna, and Chambers, Benedict J.

Published
2021

12. HIV elite control is associated with reduced TRAILshort expression.

Author

Paim, Ana C, Cummins, Nathan W, Natesampillai, Sekar, Garcia-Rivera, Enrique, Kogan, Nicole, Neogi, Ujjwal, Sönnerborg, Anders, Sperk, Maike, Bren, Gary D, Deeks, Steve, Polley, Eric, and Badley, Andrew D

Subjects
Clinical Research, Genetics, HIV/AIDS, Infection, Adult, Aged, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Prospective Studies, TNF-Related Apoptosis-Inducing Ligand, Viremia, Virus Replication, Young Adult, apoptosis, CD4(+)-positive T-lymphocytes, HIV, HIV elite controllers, TRAILshort, tumor necrosis factor-related apoptosis-inducing ligand, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology
Abstract

ObjectiveTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) dependent apoptosis has been implicated in CD4 T-cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression.DesignCohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations.MethodsTRAILshort and TRAIL gene expression in peripheral blood mononuclear cells (PBMCs) was determined by RNA-seq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively.ResultsHIV-1 elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P

Published
2019

14. Associations between integrase strand-transfer inhibitors and cardiovascular disease in people living with HIV: a multicentre prospective study from the RESPOND cohort consortium

Author

Neesgaard, Bastian, Greenberg, Lauren, Miró, Jose M, Grabmeier-Pfistershammer, Katharina, Wandeler, Gilles, Smith, Colette, De Wit, Stéphane, Wit, Ferdinand, Pelchen-Matthews, Annegret, Mussini, Cristina, Castagna, Antonella, Pradier, Christian, d'Arminio Monforte, Antonella, Vehreschild, Jörg J, Sönnerborg, Anders, Anne, Alain V, Carr, Andrew, Bansi-Matharu, Loveleen, Lundgren, Jens D, Garges, Harmony, Rogatto, Felipe, Zangerle, Robert, Günthard, Huldrych F, Rasmussen, Line D, Necsoi, Coca, van der Valk, Marc, Menozzi, Marianna, Muccini, Camilla, Peters, Lars, Mocroft, Amanda, and Ryom, Lene

Published
2022
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18. Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.

Author

Buggert, Marcus, Nguyen, Son, McLane, Laura M, Steblyanko, Maria, Anikeeva, Nadia, Paquin-Proulx, Dominic, Del Rio Estrada, Perla M, Ablanedo-Terrazas, Yuria, Noyan, Kajsa, Reuter, Morgan A, Demers, Korey, Sandberg, Johan K, Eller, Michael A, Streeck, Hendrik, Jansson, Marianne, Nowak, Piotr, Sönnerborg, Anders, Canaday, David H, Naji, Ali, Wherry, E John, Robb, Merlin L, Deeks, Steven G, Reyes-Teran, Gustavo, Sykulev, Yuri, Karlsson, Annika C, and Betts, Michael R

Subjects
Lymphoid Tissue, Lymph Nodes, CD4-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, Viral Load, Case-Control Studies, Immunologic Surveillance, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.

Published
2018

22. Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study

Author

Judd, Ali, Zangerle, Robert, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Julia, Del Amo, Obel, Niels, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella d’Arminio, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miró, Jose M, Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Quiros-Roldan, Eugenia, Sabin, Caroline, Teira, Ramon, Garrido, Myriam, Haerry, David, de Wit, Stéphane, Costagliola, Dominique, d’Arminio-Monforte, Antonella, del Amo, Julia, Raben, Dorthe, Chêne, Geneviève, Rojo, Conejo Pablo, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Grabar, Sophie, Guiguet, Marguerite, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Miro, Jose M, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, and Schomaker, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Sexually Transmitted Infections, Rare Diseases, Emerging Infectious Diseases, Infectious Diseases, HIV/AIDS, Infection, Adolescent, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cohort Studies, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Risk Factors, Sarcoma, Kaposi, Viral Load, Young Adult, AIDS-defining Cancer Project Working Group for IeDEA and COHERE in EuroCoord, HIV, Kaposi sarcoma, antiretroviral therapy, cohort study, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundWe compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America.MethodsWe included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs).ResultsWe included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were

Published
2017

23. Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals.

Author

Tauriainen, Johanna, Scharf, Lydia, Frederiksen, Juliet, Naji, Ali, Ljunggren, Hans-Gustaf, Sönnerborg, Anders, Lund, Ole, Reyes-Terán, Gustavo, Hecht, Frederick M, Deeks, Steven G, Betts, Michael R, Buggert, Marcus, and Karlsson, Annika C

Subjects
CD8-Positive T-Lymphocytes, Humans, HIV, HIV Infections, Receptors, Immunologic, Receptors, Virus, Antigens, Differentiation, T-Lymphocyte, Antiretroviral Therapy, Highly Active, Signal Transduction, Gene Expression Regulation, Adult, Middle Aged, Female, Male, Receptors, Immunologic, Virus, Antigens, Differentiation, T-Lymphocyte, Antiretroviral Therapy, Highly Active
Abstract

HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 and their ligand PVR are altered in viral infections and cancer. However, the extent to which the TIGIT/CD226/PVR-axis is affected by HIV-infection has not been characterized. Here, we report that TIGIT expression increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T cells, despite early ART. These findings highlight the importance of the TIGIT/CD226/PVR axis as an immune checkpoint barrier that could hinder future "cure" strategies requiring potent HIV-specific CD8+ T cells.

Published
2017

26. Regulating Health Data: A Comparative Perspective

Author

Catanzariti, Mariavittoria, Incardona, Francesca, Resta, Giorgio, Sönnerborg, Anders, Kofod , Nicolai Søderlund, Xiang, Wen, Catanzariti, Mariavittoria, Incardona, Francesca, Resta, Giorgio, Sönnerborg, Anders, Kofod , Nicolai Søderlund, and Xiang, Wen

Published
2024

27. Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.

Author

Giammarino, Federica, Sönnerborg, Anders, and Ceña-Diez, Rafael

Subjects
RALTEGRAVIR, EFAVIRENZ, NON-nucleoside reverse transcriptase inhibitors, HIV, ANTIRETROVIRAL agents, LONG-term non-progressors, INTEGRASE inhibitors
Abstract

Introduction: The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates. Methods: Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay's Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism. Results: WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates. Conclusion: Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV- 1 compounds. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1.

Author

Teodoro, Giulia Di, Pirkl, Martin, Incardona, Francesca, Vicenti, Ilaria, Sönnerborg, Anders, Kaiser, Rolf, Palagi, Laura, Zazzi, Maurizio, and Lengauer, Thomas

Subjects
HIV, VIRAL mutation, VIRAL load, HISTORICAL literacy, DATABASES, ANTIRETROVIRAL agents
Abstract

Motivation In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using this information (NH). Results The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Wilcoxon test results confirm significant improvement of predictive accuracy for treatment outcomes through incorporating historical information. The increased performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in acquiring mutations. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. Availability and implementation This analysis was conducted using the Euresist Integrated DataBase (EIDB). For further validation, we encourage reproducing this study with the latest release of the EIDB, which can be accessed upon request through the Euresist Network. [ABSTRACT FROM AUTHOR]

Published
2024
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30. EuCARE-HOSPITALISED Study Protocol: A Cohort Study of Patients Hospitalised with COVID-19 in the EuCARE Project

Author

Hedberg, Pontus, primary, Varisco, Benedetta, additional, Bai, Francesca, additional, Sönnerborg, Anders, additional, Naucler, Pontus, additional, Pfeifer, Nico, additional, Cozzi-Lepri, Alessandro, additional, Ceccherini-Silberstein, Francesca, additional, Naumovas, Daniel, additional, Drobniewski, Francis, additional, Jensen, Björn-Erik Ole, additional, Toscano, Cristina, additional, Parczewski, Miłosz, additional, Quintanares, Gibran Horemheb Rubio, additional, Mwau, Matilu, additional, Pinto, Jorge A., additional, Incardona, Francesca, additional, Mommo, Chiara, additional, and Marchetti, Giulia, additional

Published
2023
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32. Evaluating the Impact of Functional Genetic Variation on HIV-1 Control

Author

McLaren, Paul J., Pulit, Sara L., Gurdasani, Deepti, Bartha, Istvan, Shea, Patrick R., Pomilla, Cristina, Gupta, Namrata, Gkrania-Klotsas, Effrossyni, Young, Elizabeth H., Bannert, Norbert, Del Amo, Julia, Gill, M John, Gilmour, Jill, Kellam, Paul, Kelleher, Anthony D., Sönnerborg, Anders, Zangerle, Robert, Post, Frank A., Fisher, Martin, Haas, David W., Walker, Bruce D., Porter, Kholoud, Goldstein, David B., Sandhu, Manjinder S., de Bakker, Paul I.W., and Fellay, Jacques

Published
2017

33. Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial.

Author

Sundén-Cullberg, Jonas, Chen, Puran, Häbel, Henrike, Skorup, Paul, Janols, Helena, Rasmuson, Johan, Niward, Katarina, Östholm Balkhed, Åse, Chatzidionysiou, Katerina, Asgeirsson, Hilmir, Blennow, Ola, Parke, Åsa, Svensson, Anna-Karin, Muvva, Jagadeeswara Rao, Ljunggren, Hans-Gustav, Horne, Anna-Carin, Ådén, Ulrika, Henter, Jan-Inge, Sönnerborg, Anders, and Vesterbacka, Jan

Subjects
SEQUENTIAL analysis, ANAKINRA, TOCILIZUMAB, HOSPITAL patients, COVID-19, LACTATE dehydrogenase
Abstract

Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration. Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery. Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly. Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020–00174824). [ABSTRACT FROM AUTHOR]

Published
2023
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34. Long-term virological suppression on first-line efavirenz + tenofovir + emtricitabine/lamivudine for HIV-1

Author

Stirrup, Oliver, Sterne, Jonathan, Dunn, David T., Grabmeier-Pfistershammer, Katharina, Papastamopoulos, Vasileios, Vandenhende, Marie-Anne, Wit, Ferdinand, Porter, Kholoud, Gunsenheimer-Bartmeyer, Barbara, Jarrin, Inma, Garcia, Federico, Fätkenheuer, Gerd, Obel, Niels, Schultze, Anna, Antinori, Andrea, Ceccherini-Silberstein, Francesca, Mussini, Cristina, Chêne, Geneviève, Neesgaard, Bastian, Castagna, Antonella, Kouyos, Roger, De Wit, Stéphane, Sönnerborg, Anders, Sabin, Caroline, Merino, Dolores, Barger, Diana, and Phillips, Andrew

Published
2019
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36. Cohort profile: InfCareHIV, a prospective registry-based cohort study of people with diagnosed HIV in Sweden

Author

Carlander, Christina, primary, Brännström, Johanna, additional, Månsson, Fredrik, additional, Elvstam, Olof, additional, Albinsson, Pernilla, additional, Blom, Simon, additional, Mattsson, Lena, additional, Hovmöller, Sanne, additional, Norrgren, Hans, additional, Mellgren, Åsa, additional, Svedhem, Veronica, additional, Gisslén, Magnus, additional, and Sönnerborg, Anders, additional

Published
2023
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38. Synergistic antiviral activity against drug-resistant HIV-1 by naturally occurring dipeptide and A single-stranded oligonucleotide

Author

Ceña-Diez, Rafael, Spetz, Anna-Lena, Sönnerborg, Anders, Ceña-Diez, Rafael, Spetz, Anna-Lena, and Sönnerborg, Anders

Abstract

The novel dipeptide WG-am and single-stranded oligonucleotide combination (WG-am:ssON) showed synergistic antiviral activity against HIV-1 integrase-, protease- or reverse transcriptase drug resistant isolates, with over 95% reduction. The highest selectivity indexes were for integrase resistant isolates. WG-am:ssON can be a future option for treatment of HIV drug-resistant strains.

Published
2023
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39. Recent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV

Author

Jaschinski, Nadine, Greenberg, Lauren, Neesgaard, Bastian, Miró, Jose M., Grabmeier-Pfistershammer, Katharina, Wandeler, Gilles, Smith, Colette, De Wit, Stéphane, Wit, Ferdinand, Pelchen-Matthews, Annegret, Mussini, Cristina, Castagna, Antonella, Pradier, Christian, D'Arminio Monforte, Antonella, Vehreschild, Jörg, Sönnerborg, Anders, Anne, Alain V., Carr, Andrew, Bansi-Matharu, Loveleen, Lundgren, Jens, Garges, Harmony, Rogatto, Felipe, Zangerle, Robert, Günthard, Huldrych F., Rasmussen, Line D., Nescoi, Coca, Van Der Valk, Marc, Menozzi, Marianna, Muccini, Camilla, Mocroft, Amanda, Peters, Lars, Ryom, Lene, Jaschinski, Nadine, Greenberg, Lauren, Neesgaard, Bastian, Miró, Jose M., Grabmeier-Pfistershammer, Katharina, Wandeler, Gilles, Smith, Colette, De Wit, Stéphane, Wit, Ferdinand, Pelchen-Matthews, Annegret, Mussini, Cristina, Castagna, Antonella, Pradier, Christian, D'Arminio Monforte, Antonella, Vehreschild, Jörg, Sönnerborg, Anders, Anne, Alain V., Carr, Andrew, Bansi-Matharu, Loveleen, Lundgren, Jens, Garges, Harmony, Rogatto, Felipe, Zangerle, Robert, Günthard, Huldrych F., Rasmussen, Line D., Nescoi, Coca, Van Der Valk, Marc, Menozzi, Marianna, Muccini, Camilla, Mocroft, Amanda, Peters, Lars, and Ryom, Lene

Abstract

Objective:Assessing whether the previously reported association between abacavir (ABC) and cardiovascular disease (CVD) remained amongst contemporarily treated people with HIV.Design:Multinational cohort collaboration.Methods:RESPOND participants were followed from the latest of 1 January 2012 or cohort enrolment until the first of a CVD event (myocardial infarction, stroke, invasive cardiovascular procedure), last follow-up or 31 December 2019. Logistic regression examined the odds of starting ABC by 5-year CVD or chronic kidney disease (CKD) D:A:D risk score. We assessed associations between recent ABC use (use within the past 6 months) and risk of CVD with negative binomial regression models, adjusted for potential confounders.Results:Of 29 340 individuals, 34% recently used ABC. Compared with those at low estimated CVD and CKD risks, the odds of starting ABC were significantly higher among individuals at high CKD risk [odds ratio 1.12 (95% confidence interval = 1.04-1.21)] and significantly lower for individuals at moderate, high or very high CVD risk [0.80 (0.72-0.88), 0.75 (0.64-0.87), 0.71 (0.56-0.90), respectively]. During 6.2 years of median follow-up (interquartile range; 3.87-7.52), there were 748 CVD events (incidence rate 4.7 of 1000 persons-years of follow up (4.3-5.0)]. The adjusted CVD incidence rate ratio was higher for individuals with recent ABC use [1.40 (1.20-1.64)] compared with individuals without, consistent across sensitivity analyses. The association did not differ according to estimated CVD (interaction P = 0.56) or CKD (P = 0.98) risk strata.Conclusion:Within RESPOND's contemporarily treated population, a significant association between CVD incidence and recent ABC use was confirmed and not explained by preferential ABC use in individuals at increased CVD or CKD risk.

Published
2023

41. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

Author

SPREAD Program, Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van de Vijver, David A. M. C., Åsjȯ, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leondios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A. B., Schmit, Jean-Claude, and Wensing, Annemarie M. J.

Published
2016

46. Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV

Author

Ray, Shilpa, primary, Narayanan, Ashwathy, additional, Vesterbacka, Jan, additional, Blennow, Ola, additional, Chen, Puran, additional, Gao, Yu, additional, Gabarrini, Giorgio, additional, Ljunggren, Hans-Gustaf, additional, Buggert, Marcus, additional, Manoharan, Lokeshwaran, additional, Chen, Margaret, additional, Aleman, Soo, additional, Sönnerborg, Anders, additional, and Nowak, Piotr, additional

Published
2023
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49. Plasma HIV-1 RNA and CD4+ T-cell counts are determinants of virological non-suppression outcomes with initial integrase inhibitor-based regimens: A prospective RESPOND cohort study

Author

Álvarez, Hortensia, Mocroft, Amanda, Ryom, Lene, Neesgaard, Bastian, Edwards, Simon, Svedhem, Vero-Nica, Günthard, Huldrych F, Zangerle, Robert, Smith, Colette, Castagna, Antonella, D Arminio Monforte, Antonella, Wit, Ferdinand, Stecher, Melanie, Lehman, Clara, Mussini, Cristina, Fontas, Eric, González, Eva, Wasmuth, Jan-Christian, Sönnerborg, Anders, De Wit, Stéphane, Chkhartishvili, Nikoloz, Stephan, Christoph, Petoumenos, Kathy, Jaschinski, Nadine, Vannappagari, Vani, Gallant, Joel, Young, Lital, Volny Anne, Alain, Greenberg, Lauren, Martín-Iguacel, Raquel, Poveda, Eva, and Llibre, Josep M

Subjects
integrase inhibitors, residual viremia, virological failure, blip, low-level viremia, dolutegravir
Published
2023

50. Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia

Author

Angelis, Konstantinos, Albert, Jan, Mamais, Ioannis, Magiorkinis, Gkikas, Hatzakis, Angelos, Hamouda, Osamah, Struck, Daniel, Vercauteren, Jurgen, Wensing, Annemarie M. J., Alexiev, Ivailo, Åsjö, Birgitta, Balotta, Claudia, Camacho, Ricardo J., Coughlan, Suzie, Griskevicius, Algirdas, Grossman, Zehava, Horban, Andrzej, Kostrikis, Leondios G., Lepej, Snjezana, Liitsola, Kirsi, Linka, Marek, Nielsen, Claus, Otelea, Dan, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Schmit, Jean-Claude, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Boucher, Charles A. B., Kaplan, Lauren, Vandamme, Anne-Mieke, and Paraskevis, Dimitrios

Published
2015

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