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1. Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study

Author

Filiz, Mine, Erdem, Hakan, Ankarali, Handan, Puca, Edmond, Ruch, Yvon, Santos, Lurdes, Fasciana, Teresa, Giammanco, Anna M., Ghanem-Zoubi, Nesrin, Argemi, Xavier, Hansmann, Yves, Guner, Rahmet, Tonziello, Gilda, Mazzucotelli, Jean-Philippe, Como, Najada, Kose, Sukran, Batirel, Ayse, Inan, Asuman, Tulek, Necla, Pekok, Abdullah Umut, Khan, Ejaz Ahmed, Iyisoy, Atilla, Meric-Koc, Meliha, Kaya-Kalem, Ayse, Martins, Pedro Palma, Hasanoglu, Imran, Silva-Pinto, André, Oztoprak, Nefise, Duro, Raquel, Almajid, Fahad, Dogan, Mustafa, Dauby, Nicolas, Gunst, Jesper Damsgaard, Tekin, Recep, Konopnicki, Deborah, Petrosillo, Nicola, Bozkurt, Ilkay, Al Ramahi, Jamal Wadi, Popescu, Corneliu, Balkan, Ilker Inanc, Ozer-Balin, Safak, Zupanc, Tatjana Lejko, Cascio, Antonio, Dumitru, Irina Magdalena, Erdem, Aysegul, Ersoz, Gulden, Tasbakan, Meltem, Ajamieh, Oday Abu, Sirmatel, Fatma, Florescu, Simin, Gulsun, Serda, Ozkaya, Hacer Deniz, Sari, Sema, Tosun, Selma, Avci, Meltem, Cag, Yasemin, Celebi, Guven, Sagmak-Tartar, Ayse, Karakus, Sumeyra, Sener, Alper, Dedej, Arjeta, Oncu, Serkan, Del Vecchio, Rosa Fontana, Ozturk-Engin, Derya, and Agalar, Canan

Published
2024
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2. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

Author

Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B. H., Lau, Jillian S. Y., Copertino, Jr, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, and Søgaard, Ole S.

Published
2023
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7. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial

Author

Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I-Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D. Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, and Søgaard, Ole S.

Published
2022
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8. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial

Author

Gruell, Henning, Gunst, Jesper D, Cohen, Yehuda Z, Pahus, Marie H, Malin, Jakob J, Platten, Martin, Millard, Katrina G, Tolstrup, Martin, Jones, R Brad, Conce Alberto, Winnifer D, Lorenzi, Julio C C, Oliveira, Thiago Y, Kümmerle, Tim, Suárez, Isabelle, Unson-O'Brien, Cecilia, Nogueira, Lilian, Olesen, Rikke, Østergaard, Lars, Nielsen, Henrik, Lehmann, Clara, Nussenzweig, Michel C, Fätkenheuer, Gerd, Klein, Florian, Caskey, Marina, and Søgaard, Ole S

Published
2022
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9. Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Author

Rosás-Umbert, Miriam, Gunst, Jesper D., Pahus, Marie H., Olesen, Rikke, Schleimann, Mariane, Denton, Paul W., Ramos, Victor, Ward, Adam, Kinloch, Natalie N., Copertino, Dennis C., Escribà, Tuixent, Llano, Anuska, Brumme, Zabrina L., Brad Jones, R., Mothe, Beatriz, Brander, Christian, Fox, Julie, Nussenzweig, Michel C., Fidler, Sarah, Caskey, Marina, Tolstrup, Martin, and Søgaard, Ole S.

Published
2022
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12. Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

Author

Gunst, Jesper D., Staerke, Nina B., Pahus, Marie H., Kristensen, Lena H., Bodilsen, Jacob, Lohse, Nicolai, Dalgaard, Lars S., Brønnum, Dorthe, Fröbert, Ole, Hønge, Bo, Johansen, Isik S., Monrad, Ida, Erikstrup, Christian, Rosendal, Regitze, Vilstrup, Emil, Mariager, Theis, Bove, Dorthe G., Offersen, Rasmus, Shakar, Shakil, Cajander, Sara, Jørgensen, Nis P., Sritharan, Sajitha S., Breining, Peter, Jespersen, Søren, Mortensen, Klaus L., Jensen, Mads L., Kolte, Lilian, Frattari, Giacomo S., Larsen, Carsten S., Storgaard, Merete, Nielsen, Lars P., Tolstrup, Martin, Sædder, Eva A., Østergaard, Lars J., Ngo, Hien T.T., Jensen, Morten H., Højen, Jesper F., Kjolby, Mads, and Søgaard, Ole S.

Published
2021
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15. The impact of analytical treatment interruptions and trial interventions on time to viral re‐suppression in people living with HIV restarting ART in cure‐related clinical studies: a systematic review and meta‐analysis.

Author

Lee, Ming Jie, Eason, Miles, Castagna, Antonella, Laura, Galli, De Scheerder, Marie‐Angelique, Riley, James, Tebas, Pablo, Gunst, Jesper, Søgaard, Ole, Florence, Eric, Kroon, Eugene, De Souza, Mark, Mothe, Beatriz, Caskey, Marina, and Fidler, Sarah

Subjects
STRUCTURED treatment interruption, VIRAL load, INTEGRASE inhibitors, SCIENCE databases, WEB databases
Abstract

Introduction: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta‐analysis to identify the impact of ATI with or without novel therapeutics in cure‐related studies on the time to viral re‐suppression following ART restart. Methods: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re‐suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI‐only groups. Random‐effects proportional meta‐analysis and multivariable Cox proportional hazards analysis were performed using R. Results: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI‐only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow‐up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40–0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46–0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89–0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59–0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16–2.59). Discussion: When designing studies involving ATIs, information on time to viral re‐suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. Conclusions: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re‐suppression. [ABSTRACT FROM AUTHOR]

Published
2024
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16. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS‐CoV‐2 infection

Author

van der Sluis, Renée M, Cham, Lamin B, Gris‐Oliver, Albert, Gammelgaard, Kristine R, Pedersen, Jesper G, Idorn, Manja, Ahmadov, Ulvi, Hernandez, Sabina Sanches, Cémalovic, Ena, Godsk, Stine H, Thyrsted, Jacob, Gunst, Jesper D, Nielsen, Silke D, Jørgensen, Janni J, Bjerg, Tobias Wang, Laustsen, Anders, Reinert, Line S, Olagnier, David, Bak, Rasmus O, Kjolby, Mads, Holm, Christian K, Tolstrup, Martin, Paludan, Søren R, Kristensen, Lasse S, Søgaard, Ole S, and Jakobsen, Martin R

Published
2022
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17. Blood Culture Negative Endocarditis; What Do Concurrent Cardiac Disorders Tell Us?

Author

Filiz, Mine, primary, Erdem, Hakan, additional, Ankarali, Handan, additional, Puca, Edmond, additional, Ruch, Yvon, additional, Santos, Lurdes, additional, Ghanem-Zoubi, Nesrin, additional, Argemi, Xavier, additional, Hansmann, Yves, additional, Guner, Rahmet, additional, Tonziello, Gilda, additional, Mazzucotelli, Jean-Philippe, additional, Como, Najada, additional, Kose, Sukran, additional, Batirel, Ayse, additional, Inan, Asuman, additional, Tulek, Necla, additional, Pekok, Abdullah Umut, additional, Khan, Ejaz Ahmed, additional, Iyisoy, Atilla, additional, Meric-Koc, Meliha, additional, Kaya-Kalem, Ayse, additional, Martins, Pedro Palma, additional, Hasanoglu, Imran, additional, Silva-Pinto, André, additional, Oztoprak, Nefise, additional, Duro, Raquel, additional, Almajid, Fahad, additional, Dogan, Mustafa, additional, Dauby, Nicolas, additional, Gunst, Jesper Damsgaard, additional, Tekin, Recep, additional, Konopnicki, Deborah, additional, Petrosillo, Nicola, additional, Bozkurt, Ilkay, additional, Ramahi, Jamal Wadi Al, additional, Popescu, Corneliu, additional, Balkan, Ilker Inanc, additional, Ozer-Balin, Safak, additional, Zupanc, Tatjana Lejko, additional, Cascio, Antonio, additional, Dumitru, Irina Magdalena, additional, Erdem, Aysegul, additional, Ersoz, Gulden, additional, Tasbakan, Meltem, additional, Ajamieh, Oday Abu, additional, Sirmatel, Fatma, additional, Florescu, Simin, additional, Gulsun, Serda, additional, Ozkaya, Hacer Deniz, additional, Sari, Sema, additional, Tosun, Selma, additional, Avci, Meltem, additional, Cag, Yasemin, additional, Celebi, Guven, additional, Sagmak-Tartar, Ayse, additional, Karakus, Sumeyra, additional, Sener, Alper, additional, Dedej, Arjeta, additional, Oncu, Serkan, additional, Vecchio, Rosa Fontana Del, additional, Ozturk-Engin, Derya, additional, and Agalar, Canan, additional

Published
2024
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19. Portraying infective endocarditis: results of multinational ID-IRI study

Author

Erdem, Hakan, Puca, Edmond, Ruch, Yvon, Santos, Lurdes, Ghanem-Zoubi, Nesrin, Argemi, Xavier, Hansmann, Yves, Guner, Rahmet, Tonziello, Gilda, Mazzucotelli, Jean-Philippe, Como, Najada, Kose, Sukran, Batirel, Ayse, Inan, Asuman, Tulek, Necla, Pekok, Abdullah Umut, Khan, Ejaz Ahmed, Iyisoy, Atilla, Meric-Koc, Meliha, Kaya-Kalem, Ayse, Martins, Pedro Palma, Hasanoglu, Imran, Silva-Pinto, André, Oztoprak, Nefise, Duro, Raquel, Almajid, Fahad, Dogan, Mustafa, Dauby, Nicolas, Gunst, Jesper Damsgaard, Tekin, Recep, Konopnicki, Deborah, Petrosillo, Nicola, Bozkurt, Ilkay, Wadi, Jamal, Popescu, Corneliu, Balkan, Ilker Inanc, Ozer-Balin, Safak, Zupanc, Tatjana Lejko, Cascio, Antonio, Dumitru, Irina Magdalena, Erdem, Aysegul, Ersoz, Gulden, Tasbakan, Meltem, Ajamieh, Oday Abu, Sirmatel, Fatma, Florescu, Simin, Gulsun, Serda, Ozkaya, Hacer Deniz, Sari, Sema, Tosun, Selma, Avci, Meltem, Cag, Yasemin, Celebi, Guven, Sagmak-Tartar, Ayse, Karakus, Sumeyra, Sener, Alper, Dedej, Arjeta, Oncu, Serkan, Del Vecchio, Rosa Fontana, Ozturk-Engin, Derya, and Agalar, Canan

Published
2019
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24. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence:the randomized phase 2a TITAN trial

Author

Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B.H., Lau, Jillian S.Y., Copertino, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, Søgaard, Ole S., Gunst, Jesper D., Højen, Jesper F., Pahus, Marie H., Rosás-Umbert, Miriam, Stiksrud, Birgitte, McMahon, James H., Denton, Paul W., Nielsen, Henrik, Johansen, Isik S., Benfield, Thomas, Leth, Steffen, Gerstoft, Jan, Østergaard, Lars, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Vibholm, Line, Weis, Nina, Dyrhol-Riise, Anne M., Pedersen, Karen B.H., Lau, Jillian S.Y., Copertino, Dennis C., Linden, Noemi, Huynh, Tan T., Ramos, Victor, Jones, R. Brad, Lewin, Sharon R., Tolstrup, Martin, Rasmussen, Thomas A., Nussenzweig, Michel C., Caskey, Marina, Reikvam, Dag Henrik, and Søgaard, Ole S.

Abstract

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756., Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .

Published
2023

27. The Impact of Analytical Treatment Interruptions and Trial Interventions on Time to Viral Re-Suppression in People Living with HIV Restarting ART in Cure-Related Clinical Studies: A Systematic Review and Meta-Analysis

Author

Lee, Ming, primary, Eason, Miles, additional, Castagna, Antonella, additional, Galli, Laura, additional, De Scheerder, Marie-Angélique, additional, Riley, James L., additional, Tebas, Pablo, additional, Gunst, Jesper D., additional, Søgaard, Ole S., additional, Florence, Eric, additional, Kroon, Eugene, additional, De Souza, Mark, additional, Mothe, Beatriz, additional, Caskey, Marina, additional, and Fidler, Sarah, additional

Published
2023
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33. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1:a phase 1b/2a, randomized trial

Author

Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I. Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D.Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, Søgaard, Ole S., Gunst, Jesper D., Pahus, Marie H., Rosás-Umbert, Miriam, Lu, I. Na, Benfield, Thomas, Nielsen, Henrik, Johansen, Isik S., Mohey, Rajesh, Østergaard, Lars, Klastrup, Vibeke, Khan, Maryam, Schleimann, Mariane H., Olesen, Rikke, Støvring, Henrik, Denton, Paul W., Kinloch, Natalie N., Copertino, Dennis C., Ward, Adam R., Alberto, Winiffer D.Conce, Nielsen, Silke D., Puertas, Maria C., Ramos, Victor, Reeves, Jacqueline D., Petropoulos, Christos J., Martinez-Picado, Javier, Brumme, Zabrina L., Jones, R. Brad, Fox, Julie, Tolstrup, Martin, Nussenzweig, Michel C., Caskey, Marina, Fidler, Sarah, and Søgaard, Ole S.

Abstract

Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection (NCT03041012). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4+ T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4+ T cells and virus-specific CD8+ T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117 sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. In 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Furthermore, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4+ T cells containing intact HIV-1 provirus. At day 365, early 3BNC117 + romidepsin was associated with enhanced HIV-1 Gag-specific CD8+ T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in individuals whose pre-ART plasma HIV-1 envelope sequences were antibody sensitive. The results were not disaggregated by sex. Adverse events were

Published
2022

34. TLR2 and TLR7 mediate distinct immunopathological and antiviral plasmacytoid dendritic cell responses to SARS‐CoV‐2 infection

Author

Sluis, Renée M, primary, Cham, Lamin B, additional, Gris‐Oliver, Albert, additional, Gammelgaard, Kristine R, additional, Pedersen, Jesper G, additional, Idorn, Manja, additional, Ahmadov, Ulvi, additional, Hernandez, Sabina Sanches, additional, Cémalovic, Ena, additional, Godsk, Stine H, additional, Thyrsted, Jacob, additional, Gunst, Jesper D, additional, Nielsen, Silke D, additional, Jørgensen, Janni J, additional, Bjerg, Tobias Wang, additional, Laustsen, Anders, additional, Reinert, Line S, additional, Olagnier, David, additional, Bak, Rasmus O, additional, Kjolby, Mads, additional, Holm, Christian K, additional, Tolstrup, Martin, additional, Paludan, Søren R, additional, Kristensen, Lasse S, additional, Søgaard, Ole S, additional, and Jakobsen, Martin R, additional

Published
2022
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38. Distinct SARS-CoV-2 sensing pathways in pDCs driving TLR7-antiviral vs. TLR2-immunopathological responses in COVID-19

Author

van der Sluis, Renee M, primary, Cham, Lamin B, additional, Oliver, Alberg Gris, additional, Gammelgaard, Kristine Raaby, additional, Pedersen, Jesper Geert, additional, Idorn, Manja, additional, Ahmodov, Ulvi, additional, Hernandez, Sabina S, additional, Cemalovic, Ena, additional, Godsk, Stine H, additional, Thyrsted, Jakob, additional, Gunst, Jesper D, additional, Nielsen, Silke D, additional, Jorgensen, Janni j, additional, Bjerg, Tobias W, additional, Laustsen, Anders, additional, Reinert, Line, additional, Olagnier, David, additional, Bak, Rasmus O., additional, Kjolby, Mads, additional, Holm, Christian Kanstrup, additional, Tolstrup, Martin, additional, Paludan, Soren R., additional, Kristensen, lasse S, additional, Sogaard, Ole S, additional, and Jakobsen, Martin R, additional

Published
2021
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40. The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection

Author

Møhlenberg, Michelle, primary, Monrad, Ida, additional, Vibholm, Line K., additional, Nielsen, Stine S.F., additional, Frattari, Giacomo Schmidt, additional, Schleimann, Mariane Høgsbjerg, additional, Olesen, Rikke, additional, Kjolby, Mads, additional, Gunst, Jesper Damsgaard, additional, Søgaard, Ole Schmeltz, additional, O'Brien, Thomas R., additional, Tolstrup, Martin, additional, and Hartmann, Rune, additional

Published
2021
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44. Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity.

Author

Rosás-Umbert, Miriam, Gunst, Jesper D., Pahus, Marie H., Olesen, Rikke, Schleimann, Mariane, Denton, Paul W., Ramos, Victor, Ward, Adam, Kinloch, Natalie N., Copertino, Dennis C., Escribà, Tuixent, Llano, Anuska, Brumme, Zabrina L., Brad Jones, R., Mothe, Beatriz, Brander, Christian, Fox, Julie, Nussenzweig, Michel C., Fidler, Sarah, and Caskey, Marina

Subjects
CELLULAR immunity, IMMUNITY, IMMUNOGLOBULINS, INFECTION prevention, MONOCLONAL antibodies, HIV
Abstract

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8+ T cell responses that are associated with ART-free virologic control. Broadly neutralising anti-HIV-1 antibody (bNAb) administration in nonhuman primates has been shown to stimulate adaptive T cell-specific immunity, with infection prevention observed. In this work, the authors longitudinally analyse HIV-1 specific cellular immunity in HIV-1- infected individuals starting ART with or without adjunctive bNAb treatment. [ABSTRACT FROM AUTHOR]

Published
2022
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47. SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

Author

Nielsen, Stine SF, primary, Vibholm, Line K, additional, Monrad, Ida, additional, Olesen, Rikke, additional, Frattari, Giacomo S, additional, Pahus, Marie H, additional, Højen, Jesper F, additional, Gunst, Jesper D, additional, Erikstrup, Christian, additional, Holleufer, Andreas, additional, Hartmann, Rune, additional, Østergaard, Lars, additional, Søgaard, Ole S, additional, Schleimann, Mariane H, additional, and Tolstrup, Martin, additional

Published
2020
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49. Camostat mesylate against SARS‐CoV‐2 and COVID‐19—Rationale, dosing and safety.

Author

Breining, Peter, Frølund, Anne Lier, Højen, Jesper Falkesgaard, Gunst, Jesper Damsgaard, Staerke, Nina B., Saedder, Eva, Cases‐Thomas, Manuel, Little, Paul, Nielsen, Lars Peter, Søgaard, Ole S., and Kjolby, Mads

Subjects
COVID-19, SARS-CoV-2, MEMBRANE fusion, VIRAL envelopes, PANDEMICS, VIRAL load, PROTEOLYTIC enzymes, NEURAMINIDASE
Abstract

The coronavirus responsible for COVID‐19, SARS‐CoV‐2, utilizes a viral membrane spike protein for host cell entry. For the virus to engage in host membrane fusion, SARS‐CoV‐2 utilizes the human transmembrane surface protease, TMPRSS2, to cleave and activate the spike protein. Camostat mesylate, an orally available well‐known serine protease inhibitor, is a potent inhibitor of TMPRSS2 and has been hypothesized as a potential antiviral drug against COVID‐19. In vitro human cell and animal studies have shown that camostat mesylate inhibits virus‐cell membrane fusion and hence viral replication. In mice, camostat mesylate treatment during acute infection with influenza, also dependent on TMPRSS2, leads to a reduced viral load. The decreased viral load may be associated with an improved patient outcome. Because camostat mesylate is administered as an oral drug, it may be used in outpatients as well as inpatients at all disease stages of SARS‐CoV‐2 infection if it is shown to be an effective antiviral agent. Clinical trials are currently ongoing to test whether this well‐known drug could be repurposed and utilized to combat the current pandemic. In the following, we will review current knowledge on camostat mesylate mode of action, potential benefits as an antiviral agent and ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Published
2021
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50. Central nervous system infections in the absence of cerebrospinal fluid pleocytosis

Author

Erdem, Hakan, Ozturk-Engin, Derya, Cag, Yasemin, Senbayrak, Seniha, Inan, Asuman, Kazak, Esra, Savasci, Umit, Elaldi, Nazif, Vahaboglu, Haluk, Hasbun, Rodrigo, Nechifor, Mihai, Tireli, Hulya, Kilicoglu, Gamze, Defres, Sylviane, Gulsun, Serda, Ceran, Nurgul, Crisan, Alexandru, Johansen, Isik Somuncu, Namiduru, Mustafa, Dayan, Saim, Kayabas, Uner, Parlak, Emine, Khalifa, Ahmad, Kursun, Ebru, Sipahi, Oguz Resat, Yemisen, Mucahit, Akbulut, Ayhan, Bitirgen, Mehmet, Popovic, Natasa, Kandemir, Bahar, Luca, Catalina, Parlak, Mehmet, Stahl, Jean Paul, Pehlivanoglu, Filiz, Simeon, Soline, Ulu-Kilic, Aysegul, Yasar, Kadriye, Yilmaz, Gulden, Yilmaz, Emel, Beovic, Bojana, Catroux, Melanie, Lakatos, Botond, Sunbul, Mustafa, Oncul, Oral, Alabay, Selma, Sahin-Horasan, Elif, Kose, Sukran, Shehata, Ghaydaa, Andre, Katell, Dragovac, Gorana, Gul, Hanefi Cem, Karakas, Ahmet, Chadapaud, Stéphane, Hansmann, Yves, Harxhi, Arjan, Kirova, Valerija, Masse-Chabredier, Isabelle, Oncu, Serkan, Sener, Alper, Tekin, Recep, Deveci, Ozcan, Ozkaya, Hacer Deniz, Karabay, Oguz, Agalar, Canan, Gencer, Serap, Karahocagil, Mustafa Kasim, Karsen, Hasan, Kaya, Selcuk, Pekok, Abdullah Umut, Celen, Mustafa Kemal, Deniz, Secil, Ulug, Mehmet, Demirdal, Tuna, Guven, Tumer, Bolukcu, Sibel, Avci, Meltem, Nayman-Alpat, Saygin, Yaşar, Kadriye, Pehlivanoʇlu, Filiz, Ates-Guler, Selma, Mutlu-Yilmaz, Esmeray, Tosun, Selma, Sirmatel, Fatma, Batirel, Ayşe, Öztoprak, Nefise, Kadanali, Ayten, Turgut, Huseyin, Baran, Ali Irfan, Karaahmetoglu, Gokhan, Sunnetcioglu, Mahmut, Haykir-Solay, Asli, Denk, Affan, Ayaz, Celal, Gorenek, Levent, Larsen, Lykke, Poljak, Mario, Barsic, Bruno, Argemi, Xavier, Sørensen, Signe Maj, Bohr, Anne Lisbeth, Tattevin, Pierre, Gunst, Jesper Damsgaard, Baštáková, Lenka, Jereb, Matjaž, Chehri, Mahtab, Beraud, Guillaume, Del Vecchio, Rosa Fontana, Maresca, Mauro, Yilmaz, Hava, Sharif-Yakan, Ahmad, Kanj, Souha Shararah, Korkmaz, Fatime, Komur, Suheyla, Coskuner, Seher Ayten, Ince, Nevin, Akkoyunlu, Yasemin, Halac, Gulistan, Nemli, Salih Atakan, Ak, Oznur, Gunduz, Alper, Gozel, Mustafa G., Hatipoglu, Mustafa, Cicek-Senturk, Gonul, Akcam, Fusun Z., Inkaya, Ahmet C., Sagmak-Tartar, Ayşe, Ersoy, Yasemin, Tuncer-Ertem, Gunay, Balkan, Ilker I., Cetin, Birsen, Ersoz, Gulden, Ozgunes, Nail, Yesilkaya, Aysegul, Erturk, Ayse, Gundes, Sibel, Turhan, Vedat, Yalci, Aysun, Aydin, Emsal, Diktas, Husrev, Ulcay, Asim, Seyman, Derya, Leblebicioglu, Hakan, [Erdem, Hakan -- Savasci, Umit] Gulhane Mil Med Acad, Dept Infect Dis & Clin Microbiol, Ankara, Turkey -- [Ozturk-Engin, Derya -- Senbayrak, Seniha -- Inan, Asuman] Haydarpasa Numune Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey -- [Cag, Yasemin] Lutfi Kirdar Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey -- [Kazak, Esra] Uludag Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Bursa, Turkey -- [Elaldi, Nazif] Cumhuriyet Univ, Sch Med, Dept Infect Dis & Clin Microbiol, Sivas, Turkey -- [Vahaboglu, Haluk] Medeniyet Univ, Goztepe Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey -- [Hasbun, Rodrigo] UT Hlth McGovern Med Sch, Dept Infect Dis, Houston, TX 77030 USA, Kart Yasar, Kadriye -- 0000-0003-2963-4894, Larsen, Lykke -- 0000-0002-4113-4182, VAHABOGLU, Haluk -- 0000-0001-8217-1767, Mikrobiyoloji, OMÜ, Çukurova Üniversitesi, Uludağ Üniversitesi/Tıp Fakültesi/Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kazak, Esra, AAG-8459-2021, and Ege Üniversitesi

Subjects
0301 basic medicine, Male, Leukocytosis, 0302 clinical medicine, CSF, Encephalitis, Leukocyte, Meningitis, Pleocytosis, Neurosyphilis, Diagnosis, Pathology, Medicine, 030212 general & internal medicine, Brucella meningitis, Middle aged, biology, Meningitis, Pneumococcal, General Medicine, Middle Aged, Central nervous system infection, Tıp, ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS, medicine.anatomical_structure, Cerebrospinal fluid, Bacterial Meningitides, Cerebrospinal Fluid, Infectious diseases, Protein cerebrospinal fluid level, Pneumococcal, Female, InformationSystems_MISCELLANEOUS, Human, Microbiology (medical), 030106 microbiology, Central nervous system, Brucella, Outcomes, Cerebrospinal fluid pleocytosis, Tuberculous meningitis, Article, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Humans, lcsh:RC109-216, Leukocytosis/cerebrospinal fluid, Herpes simplex encephalitis, business.industry, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Herpetic meningoencephalitis, Central Nervous System Infections/cerebrospinal fluid, Pneumococcal meningitis, Tuberculosis, meningeal, medicine.disease, biology.organism_classification, Meningitis, Pneumococcal/cerebrospinal fluid, ComputingMethodologies_PATTERNRECOGNITION, Tuberculosis, Meningeal/cerebrospinal fluid, Clinical feature, Immunology, business, Central nervous system infections
Abstract

WOS: 000417628500023, PubMed ID: 29081366, Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated. (C) 2017 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases., Grant-A-Starr Foundation, Grant-A-Starr Foundation.

Published
2017
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