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1. TL1A–DR3 Plasma Levels Are Predictive of HIV-1 Disease Control, and DR3 Costimulation Boosts HIV-1–Specific T Cell Responses

Author

Oriol-Tordera, Bruna, Olvera, Alex, Duran-Castells, Clara, Llano, Anuska, Mothe, Beatriz, Massanella, Marta, Dalmau, Judith, Ganoza, Carmela, Sanchez, Jorge, Calle, Maria Luz, Clotet, Bonaventura, Martinez-Picado, Javier, Negredo, Eugènia, Blanco, Julià, Hartigan-O'Connor, Dennis, Brander, Christian, and Ruiz-Riol, Marta

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Genetics, Prevention, HIV/AIDS, Infectious Diseases, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Antibodies, Monoclonal, Murine-Derived, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, HIV Infections, HIV-1, Humans, Male, Mice, Receptors, Tumor Necrosis Factor, Member 25, Tumor Necrosis Factor Ligand Superfamily Member 15, Biochemistry and cell biology
Abstract

Relative control of HIV-1 infection has been linked to genetic and immune host factors. In this study, we analyzed 96 plasma proteome arrays from chronic untreated HIV-1-infected individuals using the classificatory random forest approach to discriminate between uncontrolled disease (plasma viral load [pVL] >50,000 RNA copies/ml; CD4 counts 283 cells/mm3, n = 47) and relatively controlled disease (pVL

Published
2020

2. Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study

Author

Salgado, Maria, primary, Gálvez, Cristina, additional, Nijhuis, Monique, additional, Kwon, Mi, additional, Cardozo-Ojeda, E Fabian, additional, Badiola, Jon, additional, Gorman, Matthew J, additional, Huyveneers, Laura E P, additional, Urrea, Victor, additional, Bandera, Alessandra, additional, Jensen, Björn-Erik Ole, additional, Vandekerckhove, Linos, additional, Jurado, Manuel, additional, Raj, Kavita, additional, Schulze zur Wiesch, Julian, additional, Bailén, Rebeca, additional, Eberhard, Johanna M, additional, Nabergoj, Mitja, additional, Hütter, Gero, additional, Saldaña-Moreno, Raquel, additional, Oldford, Sharon, additional, Barrett, Lisa, additional, Ramirez, Maria Luisa Montes, additional, Garba, Salisu, additional, Gupta, Ravi Kumar, additional, Revollo, Boris, additional, Ferra-Coll, Christelle, additional, Kuball, Jurgen, additional, Alter, Galit, additional, Sáez-Cirión, Asier, additional, Diez-Martin, Jose Luis, additional, Duke, Elizabeth R, additional, Schiffer, Joshua T, additional, Wensing, Annemarie, additional, Martinez-Picado, Javier, additional, Muscatello, Antonio, additional, Calmy, Alexandra, additional, Chapel, Anais, additional, Mamez, Anne-Claire, additional, Passaes, Caroline, additional, Brisseau, Clarissa, additional, Olivarria, Eduardo, additional, Knops, Elena, additional, Heger, Eva, additional, Bikhezar, Fatima, additional, Perdomo-Celis, Federico, additional, Kobbe, Guido, additional, Gabriel, Ian H, additional, Lunzen, Jan V, additional, Dalmau, Judith, additional, Martín-Carbonero, Luz, additional, Puertas, Mari Carmen, additional, Garcia-Guerrero, Mari Carmen, additional, de Scheerder, Marie-Angélique, additional, Angin, Mathieu, additional, Lübke, Nadine, additional, Balsalobre, Pascual, additional, de Paz, Raquel, additional, Kaiser, Rolf, additional, Kerre, Tessa, additional, Harrer, Thomas, additional, Luedde, Tom, additional, and Rocha, Vanderson, additional

Published
2024
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3. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection

Author

Adland, Emily, Hill, Matilda, Lavandier, Nora, Csala, Anna, Edwards, Anne, Chen, Fabian, Radkowski, Marek, Kowalska, Justyna D, Paraskevis, Dimitrios, Hatzakis, Angelos, Valenzuela-Ponce, Humberto, Pfafferott, Katja, Williams, Ian, Pellegrino, Pierre, Borrow, Persephone, Mori, Masahiko, Rockstroh, Jürgen, Prado, Julia G, Mothe, Beatriz, Dalmau, Judith, Martinez-Picado, Javier, Tudor-Williams, Gareth, Frater, John, Stryhn, Anette, Buus, Soren, Teran, Gustavo Reyes, Mallal, Simon, John, Mina, Buchbinder, Susan, Kirk, Gregory, Martin, Jeffrey, Michael, Nelson, Fellay, Jacques, Deeks, Steve, Walker, Bruce, Avila-Rios, Santiago, Cole, David, Brander, Christian, Carrington, Mary, and Goulder, Philip

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, Clinical Research, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Genes, MHC Class I, HIV Infections, HIV-1, HLA-B27 Antigen, Humans, Immunodominant Epitopes, Viral Load, gag Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, CD8(+) T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, human immunodeficiency virus, CD8+ T cell, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

Published
2018

5. Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART

Author

Blanch-Lombarte, Oscar, primary, Ouchi, Dan, additional, Jimenez-Moyano, Esther, additional, Carabelli, Julieta, additional, Marin, Miguel Angel, additional, Peña, Ruth, additional, Pelletier, Adam, additional, Talla, Aarthi, additional, Sharma, Ashish, additional, Dalmau, Judith, additional, Santos, José Ramón, additional, Sékaly, Rafick-Pierre, additional, Clotet, Bonaventura, additional, and Prado, Julia G, additional

Published
2023
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6. Author response: Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART

Author

Blanch-Lombarte, Oscar, primary, Ouchi, Dan, additional, Jimenez-Moyano, Esther, additional, Carabelli, Julieta, additional, Marin, Miguel Angel, additional, Peña, Ruth, additional, Pelletier, Adam, additional, Talla, Aarthi, additional, Sharma, Ashish, additional, Dalmau, Judith, additional, Santos, José Ramón, additional, Sékaly, Rafick-Pierre, additional, Clotet, Bonaventura, additional, and Prado, Julia G, additional

Published
2023
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7. Impact of Obefazimod on Viral Persistence, Inflammation, and Immune Activation in People With Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy

Author

Bernal, Silvia, primary, Puertas, Maria C, additional, Morón-López, Sara, additional, Cranston, Ross D, additional, Urrea, Víctor, additional, Dalmau, Judith, additional, Salgado, María, additional, Gálvez, Cristina, additional, Erkizia, Itziar, additional, McGowan, Ian, additional, Scherrer, Didier, additional, Revollo, Boris, additional, Sirera, Guillem, additional, Santos, José Ramón, additional, Clotet, Bonaventura, additional, Paredes, Roger, additional, and Martinez-Picado, Javier, additional

Published
2023
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8. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Author

McLaren, Paul J., Coulonges, Cedric, Bartha, István, Lenz, Tobias L., Deutsch, Aaron J., Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N., Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J., Gurdasani, Deepti, Haas, David W., Herbeck, Joshua T., Johnson, Eric O., Kirk, Gregory D., Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M., Mullins, James I., Obel, Niels, Poli, Guido, Sandhu, Manjinder S., Schuitemaker, Hanneke, Shea, Patrick R., Theodorou, Ioannis, Walker, Bruce D., Weintrob, Amy C., Winkler, Cheryl A., Wolinsky, Steven M., Raychaudhuri, Soumya, Goldstein, David B., Telenti, Amalio, de Bakker, Paul I. W., Zagury, Jean-François, and Fellay, Jacques

Published
2015

9. Single-cell CD8+ dynamics in PLWH uncover the depletion of TIGIT+ memory HIV-1-specific cells during long-term ART

Author

Blanch-Lombarte, Oscar, primary, Ouchi, Dan, additional, Jimenez-Moyano, Esther, additional, Carabelli, Julieta, additional, Marin, Miguel Angel, additional, Penya, Ruth, additional, Pelletier, Adam, additional, Talla, Aarthi, additional, Sharma, Ashish, additional, Dalmau, Judith, additional, Santos, Josee Ramon, additional, Sekaly, Rafick-Pierre Arunkumar, additional, Clotet, Bonaventura, additional, and Prado, Julia G, additional

Published
2022
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11. Altered T‐cell subset distribution in the viral reservoir in HIV‐1‐infected individuals with extremely low proviral DNA (LoViReTs)

Author

Gálvez, Cristina, primary, Urrea, Víctor, additional, Garcia‐Guerrero, Maria del Carmen, additional, Bernal, Sílvia, additional, Benet, Susana, additional, Mothe, Beatriz, additional, Bailón, Lucía, additional, Dalmau, Judith, additional, Martinez, Andrea, additional, Nieto, Aroa, additional, Leal, Lorna, additional, García, Felipe, additional, Clotet, Bonaventura, additional, Martinez‐Picado, Javier, additional, and Salgado, Maria, additional

Published
2022
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12. Viral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors

Author

Colomer-Lluch, Marta, primary, Kilpelainen, Athina, additional, Pernas, María, additional, Peña, Ruth, additional, Ouchi, Dan, additional, Jimenez-Moyano, Esther, additional, Dalmau, Judith, additional, Casado, Concepción, additional, López-Galíndez, Cecilio, additional, Clotet, Bonaventura, additional, Martinez-Picado, Javier, additional, and Prado, Julia G., additional

Published
2022
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13. Impact of Obefazimod on Viral Persistence, Inflammation, and Immune Activation in People With HIV on Suppressive Antiretroviral Therapy

Author

Bernal, Silvia, primary, Puertas, Maria Carmen, additional, Moron-Lopez, Sara, additional, Cranston, Ross, additional, Urrea, Victor, additional, Dalmau, Judith, additional, Salgado, María, additional, Gálvez, Cristina, additional, Erkizia, Itziar, additional, McGowan, Ian, additional, Scherrer, Didier, additional, Revollo, Boris, additional, Sirera, Guillem, additional, Santos, José Ramón, additional, Clotet, Bonaventura, additional, Paredes, Roger, additional, and Martinez-Picado, Javier, additional

Published
2022
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15. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection

Author

González-Cao, María, Morán, Teresa, Dalmau, Judith, García-Corbacho, Javier, Bracht, Jillian W. P., Bernabé Caro, Reyes, Juan-Vidal, Óscar, Castro, Javier de, Blanco, Remei, Drozdowskyj, Ana, Argilaguet, Jordi, Meyerhans, Andreas, Blanco, Julià, Prado, Julia G., Carrillo, Jorge, Clotet, Bonaventura, Massutí, Bartomeu, Provencio, Mariano, Molina-Vila, Miguel A., Mayo de las Casa, Clara, Garzon, Monica, Cao, Peng, Huang, Chung-Ying, Martínez-Picado, Javier, Rosell, Rafael, Grupo Español de Cáncer de Pulmón, AstraZeneca, European Commission, Asociación Española Contra el Cáncer, and Jiangsu Province

Abstract

[Importance] Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1–infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies., [Objective] To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection., [Design, Setting, and Participants] The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti–PD-1 or anti–PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy., [Interventions] Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects., [Main Outcomes and Measures] Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1., [Results] A total of 20 HIV-1–infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study., [Conclusions and Relevance] Durvalumab treatment was feasible and safe in HIV-1–infected patients with cancer receiving combination antiretroviral therapy. HIV-1–infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments., [Trial Registration] ClinicalTrials.gov Identifier: NCT03094286., This study was sponsored by the Spanish Lung Cancer Group (SLCG) and supported by the AstraZeneca Group. A Marie Skłodowska-Curie Innovative Training Networks European Grant (ELBA No. 765492), the Spanish Association Against Cancer (AECC) (grant No.PROYE18012ROSE), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine) supported in part the associated translational study.

Published
2020

16. The genome-wide methylation profile of CD4+ T cells from HIV-infected individuals identifies distinct patterns associated with disease progression

Author

Moron Lopez, Sara, Urrea, Victor, Dalmau, Judith, López de Heredia, Miguel, Puertas, Maria C., Ouchi, Dan, Gómez, Antonio, Passaes, Caroline, Mothe, Beatriz, Brander, Christian, Saez Cirion, Asier, Clotet i Sala, Bonaventura, Esteller, Manel, Berdasco, María, and Martinez Picado, Javier

Subjects
Cèl·lules T, HIV (Viruses), ADN, VIH (Virus), T cells, virus diseases, Epigenetics, DNA, Epigenètica
Abstract

Background: Human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in progression of HIV infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of CpG islands might modulate progression of HIV infection. Methods: 85 samples were analyzed: 21 elite controllers (EC), 21 HIV-infected subjects before combination antiretroviral therapy (cART) (viremic, 93,325 HIV-1 RNA copies/ml) and under suppressive cART (cART, median of 17 months

Published
2020

17. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection

Author

Grupo Español de Cáncer de Pulmón, AstraZeneca, European Commission, Asociación Española Contra el Cáncer, Jiangsu Province, González-Cao, María, Morán, Teresa, Dalmau, Judith, García-Corbacho, Javier, Bracht, Jillian W. P., Bernabé Caro, Reyes, Juan-Vidal, Óscar, Castro, Javier de, Blanco, Remei, Drozdowskyj, Ana, Argilaguet, Jordi, Meyerhans, Andreas, Blanco, Julià, Prado, Julia G., Carrillo, Jorge, Clotet, Bonaventura, Massutí, Bartomeu, Provencio, Mariano, Molina-Vila, Miguel A., Mayo de las Casa, Clara, Garzon, Monica, Cao, Peng, Huang, Chung-Ying, Martínez-Picado, Javier, Rosell, Rafael, Grupo Español de Cáncer de Pulmón, AstraZeneca, European Commission, Asociación Española Contra el Cáncer, Jiangsu Province, González-Cao, María, Morán, Teresa, Dalmau, Judith, García-Corbacho, Javier, Bracht, Jillian W. P., Bernabé Caro, Reyes, Juan-Vidal, Óscar, Castro, Javier de, Blanco, Remei, Drozdowskyj, Ana, Argilaguet, Jordi, Meyerhans, Andreas, Blanco, Julià, Prado, Julia G., Carrillo, Jorge, Clotet, Bonaventura, Massutí, Bartomeu, Provencio, Mariano, Molina-Vila, Miguel A., Mayo de las Casa, Clara, Garzon, Monica, Cao, Peng, Huang, Chung-Ying, Martínez-Picado, Javier, and Rosell, Rafael

Abstract

[Importance] Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1–infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies., [Objective] To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection., [Design, Setting, and Participants] The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti–PD-1 or anti–PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy., [Interventions] Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects., [Main Outcomes and Measures] Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1., [Results] A total of 20 HIV-1–infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study., [Conclusions and Relevance] Durvalumab treatment was feasible and safe in HIV-1–infected patients with cancer receiving combination antiretroviral therapy. HIV-1–infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments., [Trial Registration] ClinicalTrials.gov Identifier: NCT03094286.

Published
2020

18. Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles

Author

Benet, Susana, primary, Gálvez, Cristina, additional, Drobniewski, Francis, additional, Kontsevaya, Irina, additional, Arias, Lilibeth, additional, Monguió‐Tortajada, Marta, additional, Erkizia, Itziar, additional, Urrea, Victor, additional, Ong, Ruo‐Yan, additional, Luquin, Marina, additional, Dupont, Maeva, additional, Chojnacki, Jakub, additional, Dalmau, Judith, additional, Cardona, Paula, additional, Neyrolles, Olivier, additional, Lugo‐Villarino, Geanncarlo, additional, Vérollet, Christel, additional, Julián, Esther, additional, Furrer, Hansjakob, additional, Günthard, Huldrych F., additional, Crocker, Paul R., additional, Tapia, Gustavo, additional, Borràs, Francesc E., additional, Fellay, Jacques, additional, McLaren, Paul J., additional, Telenti, Amalio, additional, Cardona, Pere‐Joan, additional, Clotet, Bonaventura, additional, Vilaplana, Cristina, additional, Martinez‐Picado, Javier, additional, and Izquierdo‐Useros, Nuria, additional

Published
2021
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19. Abstract 929: Transcriptomic analysis of pre-treatment tissue samples to predict clinical benefit to durvalumab in HIV-infected cancer patients

Author

Bracht, Jillian Wilhelmina, primary, Gonzalez-Cao, Maria, additional, Moran, Teresa, additional, Dalmau, Judith, additional, Garcia-Corbacho, Javier, additional, Bernabe, Reyes, additional, Juan, Oscar, additional, de Castro, Javier, additional, Gimenez-Capitan, Ana, additional, Blanco, Remedios, additional, Aldeguer, Erika, additional, Rodriguez, Sonia, additional, Drozdowskyj, Ana, additional, Argilaguet, Jordi, additional, Blanco, Julian, additional, Prado, Julia, additional, Brander, Christian, additional, Carrillo, Jorge, additional, Clotet, Bonaventura, additional, Massuti, Bartomeu, additional, Provencio, Mariano, additional, Huang, Chung-Ying, additional, Mayo de las Casas, Clara, additional, Garzon, Monica, additional, Cardona, Andres Felipe, additional, Arrieta, Oscar, additional, Meyerhans, Andreas, additional, Molina-Vila, Miguel Angel, additional, Martinez-Picado, Javier, additional, and Rosell, Rafael, additional

Published
2020
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20. The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression

Author

Moron-Lopez, Sara, primary, Urrea, Victor, additional, Dalmau, Judith, additional, Lopez, Miguel, additional, Puertas, Maria C, additional, Ouchi, Dan, additional, Gómez, Antonio, additional, Passaes, Caroline, additional, Mothe, Beatriz, additional, Brander, Christian, additional, Saez-Cirion, Asier, additional, Clotet, Bonaventura, additional, Esteller, Manel, additional, Berdasco, Maria, additional, and Martinez-Picado, Javier, additional

Published
2020
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21. Extremely low viral reservoir in treated chronically HIV-1-infected individuals

Author

Gálvez, Cristina, primary, Urrea, Victor, additional, Dalmau, Judith, additional, Jimenez, Montse, additional, Clotet, Bonaventura, additional, Monceaux, Valérie, additional, Huot, Nicolas, additional, Leal, Lorna, additional, González-Soler, Victoria, additional, González-Cao, Maria, additional, Müller-Trutwin, Michaela, additional, Sáez-Cirión, Asier, additional, García, Felipe, additional, Blanco, Julià, additional, Martinez-Picado, Javier, additional, and Salgado, Maria, additional

Published
2020
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22. Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab

Author

Blanch-Lombarte, Oscar, primary, Gálvez, Cristina, additional, Revollo, Boris, additional, Jiménez-Moyano, Esther, additional, Llibre, Josep M., additional, Manzano, José Luís, additional, Boada, Aram, additional, Dalmau, Judith, additional, E. Speiser, Daniel, additional, Clotet, Bonaventura, additional, G. Prado, Julia, additional, and Martinez-Picado, Javier, additional

Published
2019
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23. The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.

Author

Moron-Lopez, Sara, Urrea, Victor, Dalmau, Judith, Lopez, Miguel, Puertas, Maria C, Ouchi, Dan, Gómez, Antonio, Passaes, Caroline, Mothe, Beatriz, Brander, Christian, Saez-Cirion, Asier, Clotet, Bonaventura, Esteller, Manel, Berdasco, Maria, and Martinez-Picado, Javier

Subjects
DNA analysis, HIV infections, DISEASE progression, PROTEINS, SEQUENCE analysis, VIRAL load, DNA methylation, GENE expression, GENOMICS, CD4 lymphocyte count, MESSENGER RNA, T cells, VIROLOGY, HIV
Abstract

Background Human genetic variation—mostly in the human leukocyte antigen (HLA) and C–C chemokine receptor type 5 (CCR5) regions—explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection. Methods In total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART. Results We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg. Conclusions Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART. [ABSTRACT FROM AUTHOR]

Published
2021
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24. Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus–related Lymphomas

Author

Muncunill, Josep, primary, Baptista, Maria-Joao, additional, Hernandez-Rodríguez, Águeda, additional, Dalmau, Judith, additional, Garcia, Olga, additional, Tapia, Gustavo, additional, Moreno, Miriam, additional, Sancho, Juan-Manuel, additional, Martínez-Picado, Javier, additional, Feliu, Evarist, additional, Mate, José-Luis, additional, Ribera, Josep-Maria, additional, and Navarro, José-Tomás, additional

Published
2018
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26. Differential Immunodominance Hierarchy of CD8 + T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection

Author

Adland, Emily, primary, Hill, Matilda, additional, Lavandier, Nora, additional, Csala, Anna, additional, Edwards, Anne, additional, Chen, Fabian, additional, Radkowski, Marek, additional, Kowalska, Justyna D., additional, Paraskevis, Dimitrios, additional, Hatzakis, Angelos, additional, Valenzuela-Ponce, Humberto, additional, Pfafferott, Katja, additional, Williams, Ian, additional, Pellegrino, Pierre, additional, Borrow, Persephone, additional, Mori, Masahiko, additional, Rockstroh, Jürgen, additional, Prado, Julia G., additional, Mothe, Beatriz, additional, Dalmau, Judith, additional, Martinez-Picado, Javier, additional, Tudor-Williams, Gareth, additional, Frater, John, additional, Stryhn, Anette, additional, Buus, Soren, additional, Teran, Gustavo Reyes, additional, Mallal, Simon, additional, John, Mina, additional, Buchbinder, Susan, additional, Kirk, Gregory, additional, Martin, Jeffrey, additional, Michael, Nelson, additional, Fellay, Jacques, additional, Deeks, Steve, additional, Walker, Bruce, additional, Avila-Rios, Santiago, additional, Cole, David, additional, Brander, Christian, additional, Carrington, Mary, additional, and Goulder, Philip, additional

Published
2018
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28. HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

Author

Pino, Maria, Erkizia, Itziar, Benet, Susana, Erikson, Elina, Fernandez Figueras, Maria Teresa, Guerrero, Dolores, Dalmau, Judith, Ouchi, Dan, Rausell, Antonio, Ciuffi, Angela, Keppler, Oliver T., Telenti, Amalio, Kräusslich, Hans-Georg, Martínez Picado, Francisco Javier, Izquierdo Useros, Nuria, and Universitat Autònoma de Barcelona

Subjects
Siglec-1, Trans-infection, HIV-1, Dendritic cells
Abstract

Altres ajuts: Red Temática Cooperativa de Investigación en SIDA (RD06/0006) i Mathilde Krim Fellowship in basic biomedical research 108676 Myeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα). Here we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection. Siglec-1 on myeloid cells could fuel novel CD4(+) T-cell infections and contribute to HIV-1 dissemination in vivo.

Published
2015

29. Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus–related Lymphomas.

Author

Muncunill, Josep, Baptista, Maria-Joao, Hernandez-Rodríguez, Águeda, Dalmau, Judith, Garcia, Olga, Tapia, Gustavo, Moreno, Miriam, Sancho, Juan-Manuel, Martínez-Picado, Javier, Feliu, Evarist, Mate, José-Luis, Ribera, Josep-Maria, and Navarro, José-Tomás

Subjects
LYMPHOMA diagnosis, HIV infection complications, BIOMARKERS, CONFIDENCE intervals, EPSTEIN-Barr virus diseases, LYMPHOMAS, POLYMERASE chain reaction, VIRAL load, HIV seroconversion, HIV seronegativity, PROGNOSIS
Abstract

Background Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. Methods EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. Results HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P <.001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P <.001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67–0.96). Conclusions Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development. [ABSTRACT FROM AUTHOR]

Published
2019
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30. Identification of Siglec-1 null individuals infected with HIV-1

Author

Martinez-Picado, Javier, McLaren, Paul J, Erkizia, Itziar, Martin, Maureen P, Benet, Susana, Rotger, Margalida, Dalmau, Judith, Ouchi, Dan, Wolinsky, Steven M, Penugonda, Sudhir, Günthard, Huldrych F, Fellay, Jacques, Carrington, Mary, Izquierdo-Useros, Nuria, Telenti, Amalio, Martinez-Picado, Javier, McLaren, Paul J, Erkizia, Itziar, Martin, Maureen P, Benet, Susana, Rotger, Margalida, Dalmau, Judith, Ouchi, Dan, Wolinsky, Steven M, Penugonda, Sudhir, Günthard, Huldrych F, Fellay, Jacques, Carrington, Mary, Izquierdo-Useros, Nuria, and Telenti, Amalio

Abstract

Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals.

Published
2016

31. Identification of Siglec-1 null individuals infected with HIV-1

Author

Martinez-Picado, Javier, primary, McLaren, Paul J., additional, Erkizia, Itziar, additional, Martin, Maureen P., additional, Benet, Susana, additional, Rotger, Margalida, additional, Dalmau, Judith, additional, Ouchi, Dan, additional, Wolinsky, Steven M., additional, Penugonda, Sudhir, additional, Günthard, Huldrych F., additional, Fellay, Jacques, additional, Carrington, Mary, additional, Izquierdo-Useros, Nuria, additional, and Telenti, Amalio, additional

Published
2016
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32. How strict is galactose restriction in adults with galactosaemia? International practice

Author

Adam, Siddig Momin, Akroyd, R., Bernabei, S., Bollhalder, S., Boocock, S., Burlina, A., Coote, T., Corthouts, K., Dalmau, Judith, Dawson, S., Defourny, S., Meyer, A., Desloovere, A., Devlin, Y., Diels, M., Dokoupil, K., Donald, S., Evans, S., Fasan, I., Ferguson, C., Ford, S., Forga, M., Gallo, G., Grünert, S.C., Heddrich-Ellerbrok, M., Heidenborg, C., Jonkers, C.F., Lefebure, K., Luyten, K., MacDonald, A., Meyer, U., Micciche, A., Müller, E., Portnoi, P., Ripley, S., Robert, C.M., Robertson, L.V., Rosenbaum-Fabian, S., Sahm, K., Schultz, Erica S, Singleton, K., Sjöqvist, E., Stoelen, L., Terry, A., Thompson, S., Timmer, C., Vande Kerckhove, K., van den Ploeg, L., Van Driessche, M., van Rijn, M., van Teeffelen-Heithoff, A., Vitoria, I., Voillot, C., Wenz, J., Westbrook, M., Wildgoose, J., Zweers, H., Adam, Siddig Momin, Akroyd, R., Bernabei, S., Bollhalder, S., Boocock, S., Burlina, A., Coote, T., Corthouts, K., Dalmau, Judith, Dawson, S., Defourny, S., Meyer, A., Desloovere, A., Devlin, Y., Diels, M., Dokoupil, K., Donald, S., Evans, S., Fasan, I., Ferguson, C., Ford, S., Forga, M., Gallo, G., Grünert, S.C., Heddrich-Ellerbrok, M., Heidenborg, C., Jonkers, C.F., Lefebure, K., Luyten, K., MacDonald, A., Meyer, U., Micciche, A., Müller, E., Portnoi, P., Ripley, S., Robert, C.M., Robertson, L.V., Rosenbaum-Fabian, S., Sahm, K., Schultz, Erica S, Singleton, K., Sjöqvist, E., Stoelen, L., Terry, A., Thompson, S., Timmer, C., Vande Kerckhove, K., van den Ploeg, L., Van Driessche, M., van Rijn, M., van Teeffelen-Heithoff, A., Vitoria, I., Voillot, C., Wenz, J., Westbrook, M., Wildgoose, J., and Zweers, H.

Published
2015

33. Practices in prescribing protein substitutes for PKU in Europe : No uniformity of approach

Author

Aguiar, A., Ahring, K., Almeida, M.F., Assoun, M., Belanger Quintana, A., Bigot, S., Bihet, G., Blom Malmberg, K., Burlina, A., Bushueva, T., Caris, A., Chan, H., Clark, Rachael A, Clark, Sue, Cochrane, B., Corthouts, K., Dalmau, Judith, Dassy, M., Meyer, A., Didycz, B., Diels, M., Dokupil, K., Dubois, S., Eftring, K., Ekengren, J., Ellerton, C., Evans, S., Faria, A., Fischer, A., Ford, S., Freisinger, P., Gizewska, M., Gokmen-Ozel, H., Gribben, J., Gunden, F., Heddrich-Ellerbrok, M., Heiber, S., Heidenborg, C., Jankowski, C., Janssen-Regelink, R.G., Jones, C.I., Jonkers, C.F., Joerg-Streller, M., Kaalund-Hansen, K., Kiss, E., Lammardo, A.M., Lang, K., Lier, D., Lilje, R., Lowry, S., Luyten, K., MacDonald, A., Meyer, U., de Moor, J., Pal, A., Robert, C.M., Robertson, L., Rocha, J.C., Rohde, C., Ross, K., Saruhan, S., Sjöqvist, E., Skeath, R., Stoelen, L., ter Horst, N.M., Terry, A., Timmer, C., Tuncer, N., Vande Kerckhove, K., van den Ploeg, L., van Rijn, M., van Spronsen, Francjan J., van Teeffelen-Heithoff, A., van Wegberg, A., van Wyk, K., Vasconcelos, C., Vitoria, I., Wildgoose, J., Webster, D., White, F.J., Zweers, H., Aguiar, A., Ahring, K., Almeida, M.F., Assoun, M., Belanger Quintana, A., Bigot, S., Bihet, G., Blom Malmberg, K., Burlina, A., Bushueva, T., Caris, A., Chan, H., Clark, Rachael A, Clark, Sue, Cochrane, B., Corthouts, K., Dalmau, Judith, Dassy, M., Meyer, A., Didycz, B., Diels, M., Dokupil, K., Dubois, S., Eftring, K., Ekengren, J., Ellerton, C., Evans, S., Faria, A., Fischer, A., Ford, S., Freisinger, P., Gizewska, M., Gokmen-Ozel, H., Gribben, J., Gunden, F., Heddrich-Ellerbrok, M., Heiber, S., Heidenborg, C., Jankowski, C., Janssen-Regelink, R.G., Jones, C.I., Jonkers, C.F., Joerg-Streller, M., Kaalund-Hansen, K., Kiss, E., Lammardo, A.M., Lang, K., Lier, D., Lilje, R., Lowry, S., Luyten, K., MacDonald, A., Meyer, U., de Moor, J., Pal, A., Robert, C.M., Robertson, L., Rocha, J.C., Rohde, C., Ross, K., Saruhan, S., Sjöqvist, E., Skeath, R., Stoelen, L., ter Horst, N.M., Terry, A., Timmer, C., Tuncer, N., Vande Kerckhove, K., van den Ploeg, L., van Rijn, M., van Spronsen, Francjan J., van Teeffelen-Heithoff, A., van Wegberg, A., van Wyk, K., Vasconcelos, C., Vitoria, I., Wildgoose, J., Webster, D., White, F.J., and Zweers, H.

Published
2015

34. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Author

McLaren, Paul J, Coulonges, Cedric, Bartha, István, Lenz, Tobias L, Deutsch, Aaron J, Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N, Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J, Gurdasani, Deepti, Haas, David W, Herbeck, Joshua T, Johnson, Eric O, Kirk, Gregory D, Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M, Mullins, James I, Obel, Niels, Poli, Guido, Sandhu, Manjinder S, Schuitemaker, Hanneke, Shea, Patrick R, Theodorou, Ioannis, Walker, Bruce D, Weintrob, Amy C, Winkler, Cheryl A, Wolinsky, Steven M, Raychaudhuri, Soumya, Goldstein, David B, Telenti, Amalio, de Bakker, Paul I W, Zagury, Jean-François, Fellay, Jacques, McLaren, Paul J, Coulonges, Cedric, Bartha, István, Lenz, Tobias L, Deutsch, Aaron J, Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N, Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J, Gurdasani, Deepti, Haas, David W, Herbeck, Joshua T, Johnson, Eric O, Kirk, Gregory D, Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M, Mullins, James I, Obel, Niels, Poli, Guido, Sandhu, Manjinder S, Schuitemaker, Hanneke, Shea, Patrick R, Theodorou, Ioannis, Walker, Bruce D, Weintrob, Amy C, Winkler, Cheryl A, Wolinsky, Steven M, Raychaudhuri, Soumya, Goldstein, David B, Telenti, Amalio, de Bakker, Paul I W, Zagury, Jean-François, and Fellay, Jacques

Published
2015

35. Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach

Author

Afdeling Dietetiek, Other research (not in main researchprogram), Aguiar, A., Ahring, K., Almeida, M.F., Assoun, M., Belanger Quintana, A., Bigot, S., Bihet, G., Blom Malmberg, K., Burlina, A., Bushueva, T., Caris, A., Chan, H., Clark, Rachael A, Clark, Sue, Cochrane, B., Corthouts, K., Dalmau, Judith, Dassy, M., Meyer, A., Didycz, B., Diels, M., Dokupil, K., Dubois, S., Eftring, K., Ekengren, J., Ellerton, C., Evans, S., Faria, A., Fischer, A., Ford, S., Freisinger, P., Gizewska, M., Gokmen-Ozel, H., Gribben, J., Gunden, F., Heddrich-Ellerbrok, M., Heiber, S., Heidenborg, C., Jankowski, C., Janssen-Regelink, R.G., Jones, C.I., Jonkers, C.F., Joerg-Streller, M., Kaalund-Hansen, K., Kiss, E., Lammardo, A.M., Lang, K., Lier, D., Lilje, R., Lowry, S., Luyten, K., MacDonald, A., Meyer, U., de Moor, J., Pal, A., Robert, C.M., Robertson, L., Rocha, J.C., Rohde, C., Ross, K., Saruhan, S., Sjöqvist, E., Skeath, R., Stoelen, L., ter Horst, N.M., Terry, A., Timmer, C., Tuncer, N., Vande Kerckhove, K., van den Ploeg, L., van Rijn, M., van Spronsen, Francjan J., van Teeffelen-Heithoff, A., van Wegberg, A., van Wyk, K., Vasconcelos, C., Vitoria, I., Wildgoose, J., Webster, D., White, F.J., Zweers, H., Afdeling Dietetiek, Other research (not in main researchprogram), Aguiar, A., Ahring, K., Almeida, M.F., Assoun, M., Belanger Quintana, A., Bigot, S., Bihet, G., Blom Malmberg, K., Burlina, A., Bushueva, T., Caris, A., Chan, H., Clark, Rachael A, Clark, Sue, Cochrane, B., Corthouts, K., Dalmau, Judith, Dassy, M., Meyer, A., Didycz, B., Diels, M., Dokupil, K., Dubois, S., Eftring, K., Ekengren, J., Ellerton, C., Evans, S., Faria, A., Fischer, A., Ford, S., Freisinger, P., Gizewska, M., Gokmen-Ozel, H., Gribben, J., Gunden, F., Heddrich-Ellerbrok, M., Heiber, S., Heidenborg, C., Jankowski, C., Janssen-Regelink, R.G., Jones, C.I., Jonkers, C.F., Joerg-Streller, M., Kaalund-Hansen, K., Kiss, E., Lammardo, A.M., Lang, K., Lier, D., Lilje, R., Lowry, S., Luyten, K., MacDonald, A., Meyer, U., de Moor, J., Pal, A., Robert, C.M., Robertson, L., Rocha, J.C., Rohde, C., Ross, K., Saruhan, S., Sjöqvist, E., Skeath, R., Stoelen, L., ter Horst, N.M., Terry, A., Timmer, C., Tuncer, N., Vande Kerckhove, K., van den Ploeg, L., van Rijn, M., van Spronsen, Francjan J., van Teeffelen-Heithoff, A., van Wegberg, A., van Wyk, K., Vasconcelos, C., Vitoria, I., Wildgoose, J., Webster, D., White, F.J., and Zweers, H.

Published
2015

36. How strict is galactose restriction in adults with galactosaemia? International practice

Author

Afdeling Dietetiek, Other research (not in main researchprogram), Adam, Siddig Momin, Akroyd, R., Bernabei, S., Bollhalder, S., Boocock, S., Burlina, A., Coote, T., Corthouts, K., Dalmau, Judith, Dawson, S., Defourny, S., Meyer, A., Desloovere, A., Devlin, Y., Diels, M., Dokoupil, K., Donald, S., Evans, S., Fasan, I., Ferguson, C., Ford, S., Forga, M., Gallo, G., Grünert, S.C., Heddrich-Ellerbrok, M., Heidenborg, C., Jonkers, C.F., Lefebure, K., Luyten, K., MacDonald, A., Meyer, U., Micciche, A., Müller, E., Portnoi, P., Ripley, S., Robert, C.M., Robertson, L.V., Rosenbaum-Fabian, S., Sahm, K., Schultz, Erica S, Singleton, K., Sjöqvist, E., Stoelen, L., Terry, A., Thompson, S., Timmer, C., Vande Kerckhove, K., van den Ploeg, L., Van Driessche, M., van Rijn, M., van Teeffelen-Heithoff, A., Vitoria, I., Voillot, C., Wenz, J., Westbrook, M., Wildgoose, J., Zweers, H., Afdeling Dietetiek, Other research (not in main researchprogram), Adam, Siddig Momin, Akroyd, R., Bernabei, S., Bollhalder, S., Boocock, S., Burlina, A., Coote, T., Corthouts, K., Dalmau, Judith, Dawson, S., Defourny, S., Meyer, A., Desloovere, A., Devlin, Y., Diels, M., Dokoupil, K., Donald, S., Evans, S., Fasan, I., Ferguson, C., Ford, S., Forga, M., Gallo, G., Grünert, S.C., Heddrich-Ellerbrok, M., Heidenborg, C., Jonkers, C.F., Lefebure, K., Luyten, K., MacDonald, A., Meyer, U., Micciche, A., Müller, E., Portnoi, P., Ripley, S., Robert, C.M., Robertson, L.V., Rosenbaum-Fabian, S., Sahm, K., Schultz, Erica S, Singleton, K., Sjöqvist, E., Stoelen, L., Terry, A., Thompson, S., Timmer, C., Vande Kerckhove, K., van den Ploeg, L., Van Driessche, M., van Rijn, M., van Teeffelen-Heithoff, A., Vitoria, I., Voillot, C., Wenz, J., Westbrook, M., Wildgoose, J., and Zweers, H.

Published
2015

37. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Author

Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, CMM Groep Kaaij, McLaren, Paul J, Coulonges, Cedric, Bartha, István, Lenz, Tobias L, Deutsch, Aaron J, Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N, Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J, Gurdasani, Deepti, Haas, David W, Herbeck, Joshua T, Johnson, Eric O, Kirk, Gregory D, Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M, Mullins, James I, Obel, Niels, Poli, Guido, Sandhu, Manjinder S, Schuitemaker, Hanneke, Shea, Patrick R, Theodorou, Ioannis, Walker, Bruce D, Weintrob, Amy C, Winkler, Cheryl A, Wolinsky, Steven M, Raychaudhuri, Soumya, Goldstein, David B, Telenti, Amalio, de Bakker, Paul I W, Zagury, Jean-François, Fellay, Jacques, Infection & Immunity, JC onderzoeksprogramma Methodologie, Cancer, CMM Groep Kaaij, McLaren, Paul J, Coulonges, Cedric, Bartha, István, Lenz, Tobias L, Deutsch, Aaron J, Bashirova, Arman, Buchbinder, Susan, Carrington, Mary N, Cossarizza, Andrea, Dalmau, Judith, De Luca, Andrea, Goedert, James J, Gurdasani, Deepti, Haas, David W, Herbeck, Joshua T, Johnson, Eric O, Kirk, Gregory D, Lambotte, Olivier, Luo, Ma, Mallal, Simon, van Manen, Daniëlle, Martinez-Picado, Javier, Meyer, Laurence, Miro, José M, Mullins, James I, Obel, Niels, Poli, Guido, Sandhu, Manjinder S, Schuitemaker, Hanneke, Shea, Patrick R, Theodorou, Ioannis, Walker, Bruce D, Weintrob, Amy C, Winkler, Cheryl A, Wolinsky, Steven M, Raychaudhuri, Soumya, Goldstein, David B, Telenti, Amalio, de Bakker, Paul I W, Zagury, Jean-François, and Fellay, Jacques

Published
2015

38. HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

Author

Pino, Maria, primary, Erkizia, Itziar, additional, Benet, Susana, additional, Erikson, Elina, additional, Fernández-Figueras, Maria Teresa, additional, Guerrero, Dolores, additional, Dalmau, Judith, additional, Ouchi, Dan, additional, Rausell, Antonio, additional, Ciuffi, Angela, additional, Keppler, Oliver T, additional, Telenti, Amalio, additional, Kräusslich, Hans-Georg, additional, Martinez-Picado, Javier, additional, and Izquierdo-Useros, Nuria, additional

Published
2015
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41. Ebv-Mir-BART11-3p, Ebv-Mir-BART9 and Ebv-Mir-BART10 Are Present in the Plasma of HIV-Infected Subjects with Lymphoma and Are Potential Lymphoma Biomarkers

Author

Muncunill, Josep, Baptista, Maria Joao, Hernandez-Rodriguez, Agueda, Dalmau, Judith, Tapia, Gustavo, Garcia, Olga, Moreno, Miriam, Sancho, Juan-Manuel, Martinez-Picado, Javier, Ribera, Josep-Maria, Feliu, Evarist, Mate, Jose-Luis, and Navarro, Jose Tomas

Abstract

Epstein Barr virus (EBV) has been implicated in the lymphomagenesis, particularly of HIV-related lymphomas. EBV-infected cells are able to share miRNAs with other cells via exosomes and certain EBV-miRNAs were found in cells not infected with the virus but from patients with increased levels of EBV copies in plasma such as HIV-infected individuals. Thus, EBV-miRNAs might be detected in the plasma and might be relevant for the diagnosis and follow-up of HIV-related lymphomas.

Published
2017
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42. The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.

Author

Moron-Lopez S, Urrea V, Dalmau J, Lopez M, Puertas MC, Ouchi D, Gómez A, Passaes C, Mothe B, Brander C, Saez-Cirion A, Clotet B, Esteller M, Berdasco M, and Martinez-Picado J

Subjects
CD4-Positive T-Lymphocytes, Disease Progression, Humans, Viremia, HIV Infections drug therapy, HIV-1 genetics
Abstract

Background: Human genetic variation-mostly in the human leukocyte antigen (HLA) and C-C chemokine receptor type 5 (CCR5) regions-explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection., Methods: In total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART., Results: We observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg., Conclusions: Our study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2021
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43. Enhancement of Antiviral CD8 + T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab.

Author

Blanch-Lombarte O, Gálvez C, Revollo B, Jiménez-Moyano E, Llibre JM, Manzano JL, Boada A, Dalmau J, E Speiser D, Clotet B, Prado JG, and Martinez-Picado J

Abstract

Background: Pembrolizumab is an immune checkpoint inhibitor against programmed cell death protein-1 (PD-1) approved for therapy in metastatic melanoma. PD-1 expression is associated with a diminished functionality in HIV-1 specific-CD8 + T cells. It is thought that PD-1 blockade could contribute to reinvigorate antiviral immunity and reduce the HIV-1 reservoir., Methods: Upon metastatic melanoma diagnosis, an HIV-1-infected individual on stable suppressive antiretroviral regimen was treated with pembrolizumab. A PET-CT was performed before and one year after pembrolizumab initiation. We monitored changes in the immunophenotype and HIV-1 specific-CD8 + T-cell responses during 36 weeks of treatment. Furthermore, we assessed changes in the viral reservoir by total HIV-1 DNA, cell-associated HIV-1 RNA, and ultrasensitive plasma viral load., Results: Complete metabolic response was achieved after pembrolizumab treatment of metastatic melanoma. Activated CD8 + T-cells expressing HLA-DR + /CD38 + transiently increased over the first nine weeks of treatment. Concomitantly, there was an augmented response of HIV-1 specific-CD8 + T cells with TNF production and poly-functionality, transitioning from TNF to an IL-2 profile. Furthermore, a transient reduction of 24% and 32% in total HIV-1 DNA was observed at weeks 3 and 27, respectively, without changes in other markers of viral persistence., Conclusions: These data demonstrate that pembrolizumab may enhance the HIV-1 specific-CD8 + T-cell response, marginally affecting the HIV-1 reservoir. A transient increase of CD8 + T-cell activation, TNF production, and poly-functionality resulted from PD-1 blockade. However, the lack of sustained changes in the viral reservoir suggests that viral reactivation is needed concomitantly with HIV-1-specific immune enhancement.

Published
2019
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