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1. Infectious disease events in people with HIV receiving kidney transplantation: Analysis of the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study

Author: Kusejko, Katharina, Kouyos, Roger D., Bernasconi, Enos, Boggian, Katia, Braun, Dominique L., Calmy, Alexandra, Cavassini, Matthias, van Delden, Christian, Furrer, Hansjakob, Garzoni, Christian, Hirsch, Hans H., Hirzel, Cedric, Manuel, Oriol, Schmid, Patrick, Khanna, Nina, Haidar, Fadi, Bonani, Marco, Golshayan, Dela, Dickenmann, Michael, Sidler, Daniel, Schnyder, Aurelia, Mueller, Nicolas J., Günthard, Huldrych F., and Schreiber, Peter W.
Published: 2024
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2. Transcriptional profile of Mycobacterium tuberculosis infection in people living with HIV

Author: Tepekule, Burcu, Jörimann, Lisa, Schenkel, Corinne D., Opitz, Lennart, Tschumi, Jasmin, Wolfensberger, Rebekka, Neumann, Kathrin, Kusejko, Katharina, Zeeb, Marius, Boeck, Lucas, Kälin, Marisa, Notter, Julia, Furrer, Hansjakob, Hoffmann, Matthias, Hirsch, Hans H., Calmy, Alexandra, Cavassini, Matthias, Labhardt, Niklaus D., Bernasconi, Enos, Oesch, Gabriela, Metzner, Karin J., Braun, Dominique L., Günthard, Huldrych F., Kouyos, Roger D., Duffy, Fergal, and Nemeth, Johannes
Published: 2024
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3. Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines

Author: Schwarzmüller, Magdalena, Lozano, Cristina, Schanz, Merle, Abela, Irene A., Grosse-Holz, Silvan, Epp, Selina, Curcio, Martina, Greshake, Jule, Rusert, Peter, Huber, Michael, Kouyos, Roger D., Günthard, Huldrych F., and Trkola, Alexandra
Published: 2024
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4. Molecular epidemiology of invasive Group A streptococcal infections before and after the COVID-19 pandemic in Switzerland

Author: Andrianaki, Angeliki M., Andreoni, Federica, Franz, Jessica, Bergada-Pijuan, Judith, Scheier, Thomas C., Duwe, Tanja, Pfister, Marc, Vostokova, Ekaterina, Seth-Smith, Helena, Roloff, Tim, Kolesnik-Goldmann, Natalia, Burkhard, Sara H., Cusini, Alexia, Karrer, Urs, Rüegg, Christian, Schibli, Adrian, Schrenzel, Jacques, Musumeci, Stefano, Kouyos, Roger D., Egli, Adrian, Brugger, Silvio D., and Zinkernagel, Annelies S.
Published: 2024
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5. Assessing immunogenicity barriers of the HIV-1 envelope trimer

Author: Maliqi, Liridona, Friedrich, Nikolas, Glögl, Matthias, Schmutz, Stefan, Schmidt, Daniel, Rusert, Peter, Schanz, Merle, Zaheri, Maryam, Pasin, Chloé, Niklaus, Cyrille, Foulkes, Caio, Reinberg, Thomas, Dreier, Birgit, Abela, Irene, Peterhoff, David, Hauser, Alexandra, Kouyos, Roger D., Günthard, Huldrych F., van Gils, Marit J., Sanders, Rogier W., Wagner, Ralf, Plückthun, Andreas, and Trkola, Alexandra
Published: 2023
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6. Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward

Author: Zeeb, Marius, Weissberg, Dana, Rampini, Silvana K., Muller, Rouven, Scheier, Thomas, Zingg, Walter, Kouyos, Roger D., and Wolfensberger, Aline
Subjects: Health risk assessment -- Methods, Medical personnel -- Health aspects -- Safety and security measures, Company distribution practices, Health
Abstract: One study found SARS-CoV-2 seroprevalence to be higher among healthcare workers (HCWs) with patient contact than among those without (1), but another study found that HCWs were less likely to [...]
Published: 2022
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7. Recommendations on data sharing in HIV drug resistance research

Author: Inzaule, Seth C., Siedner, Mark J., Little, Susan J., Avila-Rios, Santiago, Ayitewala, Alisen, Bosch, Ronald J., Calvez, Vincent, Ceccherini-Silberstein, Francesca, Charpentier, Charlotte, Descamps, Diane, Eshleman, Susan H., Fokam, Joseph, Frenkel, Lisa M., Gupta, Ravindra K., Ioannidis, John P.A., Kaleebu, Pontiano, Kantor, Rami, Kassaye, Seble G., Kosakovsky Pond, Sergei L., Kouamou, Vinie, Kouyos, Roger D., Kuritzkes, Daniel R., Lessells, Richard, Marcelin, Anne-Genevieve, Mbuagbaw, Lawrence, Minalga, Brian, Ndembi, Nicaise, Neher, Richard A., Paredes, Roger, Pillay, Deenan, Raizes, Elliot G., Rhee, Soo-Yon, Richman, Douglas D., Ruxrungtham, Kiat, Sabeti, Pardis C., Schapiro, Jonathan M., Sirivichayakul, Sunee, Steegen, Kim, Sugiura, Wataru, van Zyl, Gert U., Vandamme, Anne-Mieke, Wensing, Annemarie M.J., Wertheim, Joel O., Gunthard, Huldrych F., Jordan, Michael R., and Shafer, Robert W.
Subjects: United States. Centers for Disease Control and Prevention, United States. National Institutes of Health, Merck & Company Inc., Gilead Sciences Inc., Biological products industry, HIV (Viruses) -- Drug therapy, Rilpivirine, Drug resistance -- Drug therapy, Pharmaceutical industry, Biological sciences, World Health Organization
Abstract: Author(s): Seth C. Inzaule 1, Mark J. Siedner 2, Susan J. Little 3, Santiago Avila-Rios 4, Alisen Ayitewala 5, Ronald J. Bosch 6, Vincent Calvez 7, Francesca Ceccherini-Silberstein 8, Charlotte [...]
Published: 2023
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8. Modifiable and nonmodifiable risk factors for non-ventilator-associated hospital-acquired pneumonia identified in a retrospective cohort study

Author: Kachalov, Viacheslav N., Kuster, Stefan P., Balakrishna, Suraj, Schreiber, Peter W., Jakob, Werner, Sax, Hugo, Kouyos, Roger D., and Wolfensberger, Aline
Published: 2022
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9. Quantification of transgene expression in GSH AAVS1 with a novel CRISPR/Cas9-based approach reveals high transcriptional variation

Author: Inderbitzin, Anne, Loosli, Tom, Kouyos, Roger D., and Metzner, Karin J.
Published: 2022
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10. The impact of public health interventions on the future prevalence of ESBL-producing Klebsiella pneumoniae: a population based mathematical modelling study

Author: Salazar-Vizcaya, Luisa, Atkinson, Andrew, Kronenberg, Andreas, Plüss-Suard, Catherine, Kouyos, Roger D., Kachalov, Viacheslav, Troillet, Nicolas, Marschall, Jonas, and Sommerstein, Rami
Published: 2022
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11. Assessing the Role of Bacterial Innate and Adaptive Immunity as Barriers to Conjugative Plasmids.

Author: Siedentop, Berit, Mediavilla, Carlota Losa, Kouyos, Roger D, Bonhoeffer, Sebastian, and Chabas, Hélène
Abstract: Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that restriction modification and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, restriction modification and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction. [ABSTRACT FROM AUTHOR]
Published: 2024
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12. Gender Disparities in Statin Prescriptions in People With HIV With Low/Moderate to High Cardiovascular Risk.

Author: Abela, Irene A, Chammartin, Frédérique, Amstutz, Alain, Surial, Bernard, Ballif, Marie, Marzolini, Catia, Aebi-Popp, Karoline, Notter, Julia, Segeral, Olivier, Stoeckle, Marcel, Cavassini, Matthias, Bernasconi, Enos, Günthard, Huldrych F, Kouyos, Roger D, Pasin, Chloé, and Study, the Swiss HIV Cohort
Subjects: HIV-positive persons, GENDER inequality, CISGENDER people, CARDIOVASCULAR diseases, STATINS (Cardiovascular agents)
Abstract: The REPRIEVE trial suggests that primary cardiovascular disease (CVD) prevention could be considered among people with HIV at low CVD risk. We found cisgender women with low/moderate and high CVD risk are less likely to receive statins than cisgender men. Efforts are needed to guarantee equal access to statin-based CVD prevention. [ABSTRACT FROM AUTHOR]
Published: 2024
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13. Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection

Author: Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Frischknecht, Paul, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leeman, Christine, Notter, Julia, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Frischknecht, Paul, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leeman, Christine, Notter, Julia, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, and Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348
Abstract: HIV-1 RNA genetic diversity predicts time since infection which is important for clinical care and research. It's unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose. We tested whether proviral genetic diversity from NGS sequences predicts time since infection and recency in 221 people with HIV-1 with known infection time. Proviral diversity was significantly associated with time since infection (p<5*10-07, R2 up to 25%) and predictive of treatment initiation during recent infection (AUC-ROC up to 0.85). This shows the utility of proviral genetic diversity as a proxy for time since infection.
Published: 2024

14. Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

Author: Dandekar, Satya, Dandekar, S ( Satya ), Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Ulyte, Agne; https://orcid.org/0000-0001-7419-9778, Radtke, Thomas; https://orcid.org/0000-0002-1723-1070, Haile, Sarah R; https://orcid.org/0000-0002-4704-6570, Ammann, Priska, Raineri, Alessia; https://orcid.org/0009-0007-7128-9656, Rueegg, Sonja, Epp, Selina, Berger, Christoph; https://orcid.org/0000-0002-2373-8804, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Manrique, Amapola; https://orcid.org/0000-0003-3982-398X, Audigé, Annette, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Fehr, Jan; https://orcid.org/0000-0003-1113-9895, Weber, Jacqueline, Rusert, Peter, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Puhan, Milo A; https://orcid.org/0000-0003-4721-1879, Kriemler, Susi; https://orcid.org/0000-0002-3384-7940, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Dandekar, Satya, Dandekar, S ( Satya ), Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Ulyte, Agne; https://orcid.org/0000-0001-7419-9778, Radtke, Thomas; https://orcid.org/0000-0002-1723-1070, Haile, Sarah R; https://orcid.org/0000-0002-4704-6570, Ammann, Priska, Raineri, Alessia; https://orcid.org/0009-0007-7128-9656, Rueegg, Sonja, Epp, Selina, Berger, Christoph; https://orcid.org/0000-0002-2373-8804, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Manrique, Amapola; https://orcid.org/0000-0003-3982-398X, Audigé, Annette, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Fehr, Jan; https://orcid.org/0000-0003-1113-9895, Weber, Jacqueline, Rusert, Peter, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Puhan, Milo A; https://orcid.org/0000-0003-4721-1879, Kriemler, Susi; https://orcid.org/0000-0002-3384-7940, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, and Pasin, Chloé; https://orcid.org/0000-0001-8730-790X
Abstract: Knowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020–2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.
Published: 2024

15. Do Infectious Diseases After Kidney Retransplantation Differ From Those After First Kidney Transplantation?

Author: Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Neofytos, Dionysios; https://orcid.org/0000-0001-6970-2869, van Delden, Christian; https://orcid.org/0000-0002-2901-8285, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Meylan, Pascal, Boggian, Katia, Hirzel, Cédric; https://orcid.org/0000-0002-7870-912X, Garzoni, Christian; https://orcid.org/0000-0002-0832-2376, Sidler, Daniel; https://orcid.org/0000-0002-2435-5936, Schnyder, Aurelia, Schaub, Stefan; https://orcid.org/0000-0002-9170-1341, Golshayan, Déla, Haidar, Fadi, Bonani, Marco, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Swiss Transplant Cohort Study, et al, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Neofytos, Dionysios; https://orcid.org/0000-0001-6970-2869, van Delden, Christian; https://orcid.org/0000-0002-2901-8285, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Meylan, Pascal, Boggian, Katia, Hirzel, Cédric; https://orcid.org/0000-0002-7870-912X, Garzoni, Christian; https://orcid.org/0000-0002-0832-2376, Sidler, Daniel; https://orcid.org/0000-0002-2435-5936, Schnyder, Aurelia, Schaub, Stefan; https://orcid.org/0000-0002-9170-1341, Golshayan, Déla, Haidar, Fadi, Bonani, Marco, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Swiss Transplant Cohort Study, and et al
Abstract: Background Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results A total of 59 patients with a median age of 47 years (range, 18–73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P = .02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P = .11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P < .001). Conclusions ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx.
Published: 2024

16. Cohort Profile: The Zurich Primary HIV Infection Study

Author: Freind, Matt C, Tallón de Lara, Carmen, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Wimmersberger, David, Kuster, Hebert; https://orcid.org/0000-0001-6873-0091, Aceto, Leonardo, Kovari, Helen, Flepp, Markus, Schibli, Adrian; https://orcid.org/0009-0009-5170-0254, Hampel, Benjamin, Grube, Christina, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Freind, Matt C, Tallón de Lara, Carmen, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Wimmersberger, David, Kuster, Hebert; https://orcid.org/0000-0001-6873-0091, Aceto, Leonardo, Kovari, Helen, Flepp, Markus, Schibli, Adrian; https://orcid.org/0009-0009-5170-0254, Hampel, Benjamin, Grube, Christina, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, and Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723
Abstract: The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking. By the end of December 2022, 486 people were enrolled, of which 353 were still undergoing active follow-up. Of the 486 participants, 86% had an acute infection, and 14% a recent HIV-1 infection. Men who have sex with men accounted for 74% of the study population. The median time from the estimated date of infection to diagnosis was 32 days. The median time from diagnosis to the initiation of antiretroviral therapy was 11 days, and this has consistently decreased over the last two decades. During the seroconversion phase, 447 (92%) patients reported having symptoms, of which only 73% of the patients were classified as having typical acute retroviral syndrome. The ZPHI study is a well-characterized cohort belonging to the most extensively studied primary HIV infection cohort. Its findings contribute to advancing our understanding of the early stages of HIV infection and pathogenesis, and it is paving the way to further improve HIV translational research and HIV medicine.
Published: 2024

17. Deciphering factors linked with reduced SARS-CoV-2 susceptibility in the Swiss HIV Cohort Study

Author: Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Epp, Selina, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Battegay, Manuel; https://orcid.org/0000-0002-6638-3679, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Perreau, Matthieu, Ramette, Alban; https://orcid.org/0000-0002-3437-4639, Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Marconato, Maddalena, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Swiss HIV Cohort Study, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Epp, Selina, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Battegay, Manuel; https://orcid.org/0000-0002-6638-3679, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Perreau, Matthieu, Ramette, Alban; https://orcid.org/0000-0002-3437-4639, Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Marconato, Maddalena, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Swiss HIV Cohort Study
Abstract: BACKGROUND Factors influencing susceptibility to SARS-CoV-2 remain to be resolved. Using data of the Swiss HIV Cohort Study (SHCS) on 6,270 people with HIV (PWH) and serologic assessment for SARS-CoV-2 and circulating-human-coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS We analyzed SARS-CoV-2 PCR-tests, COVID-19 related hospitalizations, and deaths reported to the SHCS between January 1, 2020 and December 31, 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in pre-pandemic (2019) and pandemic (2020) bio-banked plasma and compared to HIV-negative individuals. We applied logistic regression, conditional logistic regression, and Bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and Ab responses to SARS-CoV-2 in PWH. RESULTS No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High pre-pandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses upon infection. We observed a robust protective effect of smoking on SARS-CoV-2-infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14), which occurred even in previous smokers, and was highest for heavy smokers. CONCLUSIONS Our findings of two independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.
Published: 2024

18. Incidence of sexually transmitted infections and association with behavioural factors: Time-to-event analysis of a large pre-exposure prophylaxis (PrEP) cohort

Author: Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Schmidt, Axel J; https://orcid.org/0000-0002-6910-4399, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Christinet, Vanessa, Darling, Katharine E A; https://orcid.org/0000-0003-1449-3873, Depmeier, Carsten, Läuchli, Severin, Reinacher, Matthias, Rasi, Manuela, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bruggmann, Philip, Haerry, David, Bize, Raphaël; https://orcid.org/0000-0001-5626-4628, Low, Nicola; https://orcid.org/0000-0003-4817-8986, Vock, Florian, El Amari, Emmanuelle Boffi, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Bosshard, Philipp P; https://orcid.org/0000-0002-1154-2281, Fehr, Jan S, Hampel, Benjamin, SwissPrEPared Cohort Study, Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Schmidt, Axel J; https://orcid.org/0000-0002-6910-4399, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Christinet, Vanessa, Darling, Katharine E A; https://orcid.org/0000-0003-1449-3873, Depmeier, Carsten, Läuchli, Severin, Reinacher, Matthias, Rasi, Manuela, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bruggmann, Philip, Haerry, David, Bize, Raphaël; https://orcid.org/0000-0001-5626-4628, Low, Nicola; https://orcid.org/0000-0003-4817-8986, Vock, Florian, El Amari, Emmanuelle Boffi, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Bosshard, Philipp P; https://orcid.org/0000-0002-1154-2281, Fehr, Jan S, Hampel, Benjamin, and SwissPrEPared Cohort Study
Abstract: OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.
Published: 2024

19. Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen.

Author: Neuner-Jehle, Nadia, Zeeb, Marius, Thorball, Christian W., Fellay, Jacques, Metzner, Karin J., Frischknecht, Paul, Neumann, Kathrin, Leeman, Christine, Rauch, Andri, Stöckle, Marcel, Huber, Michael, Perreau, Matthieu, Bernasconi, Enos, Notter, Julia, Hoffmann, Matthias, Leuzinger, Karoline, Günthard, Huldrych F., Pasin, Chloé, and Kouyos, Roger D.
Subjects: HLA histocompatibility antigens, WHOLE genome sequencing, VIRAL load, IMMUNE recognition, VIRAL mutation
Abstract: The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis. Author summary: The intricate interplay between viruses and the human immune system is reflected in dynamic associations between the viral and the human genomes. These often take the form of escape dynamics, in which the virus acquires mutations that allow it to evade immune recognition. We developed a novel viral diversity-based method to screen for such interactions across the viral genome systematically and applied it to a unique dataset of HIV-1 sequences and human leukocyte antigen (HLA) variants. We could identify time-dependent interactions between 98 pairs of HLA and viral variants. Among these pairs, 12 were associated with the concentration of viral RNA, longitudinal time-to-event analyses confirmed 28, and 48 were consistent with computational predictions of viral peptide binding to HLA molecules. Our results highlight how the highly dynamic interaction between the viral genome and the immune system shapes viral evolution, and our approach offers new opportunities to systematically study such interactions from real-world cross-sectional data. [ABSTRACT FROM AUTHOR]
Published: 2024
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20. Similar But Different: Integrated Phylogenetic Analysis of Austrian and Swiss HIV-1 Sequences Reveal Differences in Transmission Patterns of the Local HIV-1 Epidemics

Author: Kusejko, Katharina, Tschumi, Nadine, Chaudron, Sandra E., Nguyen, Huyen, Battegay, Manuel, Bernasconi, Enos, Böni, Jürg, Huber, Michael, Calmy, Alexandra, Cavassini, Matthias, Egle, Alexander, Grabmeier-Pfistershammer, Katharina, Haas, Bernhard, Hirsch, Hans, Klimkait, Thomas, Öllinger, Angela, Perreau, Matthieu, Ramette, Alban, Flury, Baharak Babouee, Sarcletti, Mario, Scherrer, Alexandra, Schmid, Patrick, Yerly, Sabine, Zangerle, Robert, Günthard, Huldrych F., and Kouyos, Roger D.
Published: 2022
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21. Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

Author: Abela, Irene A., primary, Schwarzmüller, Magdalena, additional, Ulyte, Agne, additional, Radtke, Thomas, additional, Haile, Sarah R., additional, Ammann, Priska, additional, Raineri, Alessia, additional, Rueegg, Sonja, additional, Epp, Selina, additional, Berger, Christoph, additional, Böni, Jürg, additional, Manrique, Amapola, additional, Audigé, Annette, additional, Huber, Michael, additional, Schreiber, Peter W., additional, Scheier, Thomas, additional, Fehr, Jan, additional, Weber, Jacqueline, additional, Rusert, Peter, additional, Günthard, Huldrych F., additional, Kouyos, Roger D., additional, Puhan, Milo A., additional, Kriemler, Susi, additional, Trkola, Alexandra, additional, and Pasin, Chloé, additional
Published: 2024
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22. Cohort Profile: The Zurich Primary HIV Infection Study

Author: Freind, Matt C., primary, Tallón de Lara, Carmen, additional, Kouyos, Roger D., additional, Wimmersberger, David, additional, Kuster, Hebert, additional, Aceto, Leonardo, additional, Kovari, Helen, additional, Flepp, Markus, additional, Schibli, Adrian, additional, Hampel, Benjamin, additional, Grube, Christina, additional, Braun, Dominique L., additional, and Günthard, Huldrych F., additional
Published: 2024
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23. Quantifying the impact of treatment history on plasmid-mediated resistance evolution in human gut microbiota

Author: Tepekule, Burcu, zur Wiesch, Pia Abel, Kouyos, Roger D., and Bonhoeffe, Sebastian
Published: 2019

24. Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization

Author: Friedrich, Nikolas, Stiegeler, Emanuel, Glögl, Matthias, Lemmin, Thomas, Hansen, Simon, Kadelka, Claus, Wu, Yufan, Ernst, Patrick, Maliqi, Liridona, Foulkes, Caio, Morin, Mylène, Eroglu, Mustafa, Liechti, Thomas, Ivan, Branislav, Reinberg, Thomas, Schaefer, Jonas V., Karakus, Umut, Ursprung, Stephan, Mann, Axel, Rusert, Peter, Kouyos, Roger D., Robinson, John A., Günthard, Huldrych F., Plückthun, Andreas, and Trkola, Alexandra
Published: 2021
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25. Correction to: Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study

Author: Riou, Julien, Dupont, Carole, Bertagnolio, Silvia, Gupta, Ravindra K., Kouyos, Roger D., Egger, Matthias, and Althaus, Christian L.
Published: 2021
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26. Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study

Author: Riou, Julien, Dupont, Carole, Bertagnolio, Silvia, Gupta, Ravindra K., Kouyos, Roger D., Egger, Matthias, and L. Althaus, Christian
Published: 2021
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27. Author Correction: Efficient microbial colony growth dynamics quantification with ColTapp, an automated image analysis application

Author: Bär, Julian, Boumasmoud, Mathilde, Kouyos, Roger D., Zinkernagel, Annelies S., and Vulin, Clément
Published: 2021
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28. Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity

Author: Abela, Irene A., Pasin, Chloé, Schwarzmüller, Magdalena, Epp, Selina, Sickmann, Michèle E., Schanz, Merle M., Rusert, Peter, Weber, Jacqueline, Schmutz, Stefan, Audigé, Annette, Maliqi, Liridona, Hunziker, Annika, Hesselman, Maria C., Niklaus, Cyrille R., Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Karrer, Urs, Wolfensberger, Aline, Rampini, Silvana K., Meyer Sauteur, Patrick M., Berger, Christoph, Huber, Michael, Böni, Jürg, Braun, Dominique L., Marconato, Maddalena, Manz, Markus G., Frey, Beat M., Günthard, Huldrych F., Kouyos, Roger D., and Trkola, Alexandra
Published: 2021
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29. Impact of an electronic alert on prescription patterns of meropenem, voriconazole and caspofungin

Author: Chok, Lionel, Kusejko, Katharina, Eberhard, Nadia, Chaudron, Sandra E., Saleschus, Dirk, Kocher, Claudine, Kouyos, Roger D., Weber, Rainer, and Kuster, Stefan P.
Published: 2021
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30. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Author: Marconato, Maddalena, Abela, Irene A., Hauser, Anthony, Schwarzmuller, Magdalena, Katzensteiner, Rheliana, Braun, Dominique L., Epp, Selina, Audige, Annette, Weber, Jacqueline, Schindler, Emery, Ruser, Peter, Pasin, Chloe, Boni, Jurg, West, Emily, Kufner, Verena, Huber, Michael, Zaheri, Maryam, Schmutz, Stefan, Frey, Beat M., Kouyos, Roger D., Gunthard, Huldrych F., Manz, Markus G., and Trkola, Alexandra
Subjects: Viral antibodies -- Health aspects, Antibodies -- Health aspects, Health care industry
Abstract: BACKGROUND. Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated. METHODS. We conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends. RESULTS. In this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034). CONCLUSION. Our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies. TRIAL REGISTRATION. ClinicalTrials.gov NCT04869072. FUNDING. This study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Gluckskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program 'Comprehensive Genomic Pathogen Detection' of the University of Zurich., Introduction Neutralizing antibodies are recognized as a principal correlate for protection induced by SARS-CoV-2 vaccines (1, 2) and have been used for antiviral treatment as the active component in convalescent [...]
Published: 2022
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31. The path of least resistance: aggressive or moderate treatment?

Author: Kouyos, Roger D, Metcalf, C Jessica E, Birger, Ruthie, Klein, Eili Y, Wiesch, Pia Abel zur, Ankomah, Peter, Arinaminpathy, Nimalan, Bogich, Tiffany L, Bonhoeffer, Sebastian, Brower, Charles, Chi-Johnston, Geoffrey, Cohen, Ted, Day, Troy, Greenhouse, Bryan, Huijben, Silvie, Metlay, Joshua, Mideo, Nicole, Pollitt, Laura C, Read, Andrew F, Smith, David L, Standley, Claire, Wale, Nina, and Grenfell, Bryan
Subjects: Emerging Infectious Diseases, Antimicrobial Resistance, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Anti-Infective Agents, Biological Evolution, Drug Resistance, Microbial, Humans, Infections, Microbiota, drug resistance, evolution, treatment strategies, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences
Abstract: The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.
Published: 2014

32. Do Infectious Diseases After Kidney Retransplantation Differ From Those After First Kidney Transplantation?

Author: Kusejko, Katharina, Neofytos, Dionysios, Delden, Christian van, Hirsch, Hans H, Meylan, Pascal, Boggian, Katia, Hirzel, Cedric, Garzoni, Christian, Sidler, Daniel, Schnyder, Aurelia, Schaub, Stefan, Golshayan, Déla, Haidar, Fadi, Bonani, Marco, Kouyos, Roger D, Mueller, Nicolas J, Schreiber, Peter W, and Study, the Swiss Transplant Cohort
Abstract: Background Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression. Methods We included adult patients with records on f-K-Tx and re-K-Tx in the Swiss Transplant Cohort Study. We analyzed ID events after f-K-Tx and re-K-Tx within the same patients and compared infection rates, causative pathogens, and infection sites. Recurrent time-to-event analyses were performed for comparison of infection rates. Results A total of 59 patients with a median age of 47 years (range, 18–73) were included. Overall, 312 ID events in 52 patients occurred. In multivariable recurrent event modeling, the rate of ID events was significantly lower after re-K-Tx (hazard ratio, 0.70; P =.02). More bacterial (68.9% vs 60.4%) and fungal (4.0% vs 1.1%) infections were observed after f-K-Tx but fewer viral infections (27.0% vs 38.5%) as compared with re-K-Tx (P =.11). After f-K-Tx, urinary and gastrointestinal tract infections were more frequent; after re-K-Tx, respiratory tract and surgical site infections were more frequent (P <.001). Conclusions ID events were less frequent after re-K-Tx. Affected sites differed significantly after f-K-Tx vs re-K-Tx. [ABSTRACT FROM AUTHOR]
Published: 2024
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33. Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations

Author: Bär, Julian, Boumasmoud, Mathilde, Mairpady Shambat, Srikanth, Vulin, Clément, Huemer, Markus, Schweizer, Tiziano A., Gómez-Mejia, Alejandro, Eberhard, Nadia, Achermann, Yvonne, Zingg, Patrick O., Mestres, Carlos A., Brugger, Silvio D., Schuepbach, Reto A., Kouyos, Roger D., Hasse, Barbara, and Zinkernagel, Annelies S.
Published: 2022
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34. Host genomics of the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment

Author: Thorball, Christian W., Borghesi, Alessandro, Bachmann, Nadine, Von Siebenthal, Chantal, Vongrad, Valentina, Turk, Teja, Neumann, Kathrin, Beerenwinkel, Niko, Bogojeska, Jasmina, Roth, Volker, Kok, Yik Lim, Parbhoo, Sonali, Wieser, Mario, Böni, Jürg, Perreau, Matthieu, Klimkait, Thomas, Yerly, Sabine, Battegay, Manuel, Rauch, Andri, Schmid, Patrick, Bernasconi, Enos, Cavassini, Matthias, Kouyos, Roger D., Günthard, Huldrych F., Metzner, Karin J., and Fellay, Jacques
Published: 2020
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35. Antibody Response to SARS-CoV-2 Vaccination in Patients following Allogeneic Hematopoietic Cell Transplantation

Author: Huang, Alice, Cicin-Sain, Caroline, Pasin, Chloe, Epp, Selina, Audigé, Annette, Müller, Nicolas J., Nilsson, Jakob, Bankova, Andriyana, Wolfensberger, Nathan, Vilinovszki, Oliver, Nair, Gayathri, Hockl, Philipp, Schanz, Urs, Kouyos, Roger D., Hasse, Barbara, Zinkernagel, Annelies S., Trkola, Alexandra, Manz, Markus G., Abela, Irene A., and Müller, Antonia M.S.
Published: 2022
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36. Efficient microbial colony growth dynamics quantification with ColTapp, an automated image analysis application

Author: Bär, Julian, Boumasmoud, Mathilde, Kouyos, Roger D., Zinkernagel, Annelies S., and Vulin, Clément
Published: 2020
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37. Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications

Author: Pasin, Chloé, primary, Consiglio, Camila R., additional, Huisman, Jana S., additional, de Lange, Ann-Marie G., additional, Peckham, Hannah, additional, Vallejo-Yagüe, Enriqueta, additional, Abela, Irene A., additional, Islander, Ulrika, additional, Neuner-Jehle, Nadia, additional, Pujantell, Maria, additional, Roth, Olivia, additional, Schirmer, Melanie, additional, Tepekule, Burcu, additional, Zeeb, Marius, additional, Hachfeld, Anna, additional, Aebi-Popp, Karoline, additional, Kouyos, Roger D., additional, and Bonhoeffer, Sebastian, additional
Published: 2023
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38. Seroprofiling of antibodies against endemic human coronaviruses and SARS-CoV-2 in an HIV cohort in Lesotho: correlates of antibody response and seropositivity

Author: Brown, Jennifer A, Hauser, Anthony, Abela, Irene A, Pasin, Chloé, Epp, Selina, Mohloanyane, Tsepang, Nsakala, Bienvenu L, Trkola, Alexandra, Labhardt, Niklaus D, Kouyos, Roger D, and Günthard, Huldrych F
Subjects: 360 Social problems & social services, 610 Medicine & health
Abstract: BACKGROUND Serological data on endemic human coronaviruses (HCoVs) and SARS-CoV-2 in southern Africa are scarce. Here, we report on i) endemic HCoV seasonality, ii) SARS-CoV-2 seroprevalence, and iii) predictive factors for SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and HCoV serological response during a 17-month period at the start of the COVID-19 pandemic among adults living with HIV. METHODS Plasma samples were collected from February 2020 to July 2021 within an outpatient HIV cohort in Lesotho. We used the ABCORA multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS Results of 3'173 samples from 1'403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter/spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex (p = 0.004), obesity (p
Published: 2023

39. Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years

Author: Schoepf, Isabella C, primary, Esteban-Cantos, Andrés, additional, Thorball, Christian W, additional, Rodés, Berta, additional, Reiss, Peter, additional, Rodríguez-Centeno, Javier, additional, Riebensahm, Carlotta, additional, Braun, Dominique L, additional, Marzolini, Catia, additional, Seneghini, Marco, additional, Bernasconi, Enos, additional, Cavassini, Matthias, additional, Buvelot, Hélène, additional, Thurnheer, Maria Christine, additional, Kouyos, Roger D, additional, Fellay, Jacques, additional, Günthard, Huldrych F, additional, Arribas, José R, additional, Ledergerber, Bruno, additional, and Tarr, Philip E, additional
Published: 2023
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40. Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study

Author: Schwenke, Johannes M, Thorball, Christian W, Schoepf, Isabella C, Ryom, Lene, Hasse, Barbara, Lamy, Olivier, Calmy, Alexandra, Wandeler, Gilles, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Kahlert, Christian R, Bernasconi, Enos, Kouyos, Roger D, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Ledergerber, Bruno, Fellay, Jacques, Burkhalter, Felix, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Swiss HIV Cohort Study, Schwenke, Johannes M, Thorball, Christian W, Schoepf, Isabella C, Ryom, Lene, Hasse, Barbara, Lamy, Olivier, Calmy, Alexandra, Wandeler, Gilles, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Kahlert, Christian R, Bernasconi, Enos, Kouyos, Roger D, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Ledergerber, Bruno, Fellay, Jacques, Burkhalter, Felix, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, and Swiss HIV Cohort Study
Abstract: BACKGROUND Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. METHODS Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. RESULTS We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9). CONCLUSIONS In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.
Published: 2023

41. Recommendations on data sharing in HIV drug resistance research

Author: Inzaule, Seth C, Siedner, Mark J; https://orcid.org/0000-0003-3506-842X, Little, Susan J; https://orcid.org/0000-0002-7645-9737, Avila-Rios, Santiago; https://orcid.org/0000-0003-3371-4248, Ayitewala, Alisen, Bosch, Ronald J, Calvez, Vincent, Ceccherini-Silberstein, Francesca, Charpentier, Charlotte; https://orcid.org/0000-0002-6441-7054, Descamps, Diane, Eshleman, Susan H; https://orcid.org/0000-0002-4587-791X, Fokam, Joseph; https://orcid.org/0000-0002-1501-2763, Frenkel, Lisa M; https://orcid.org/0000-0001-9566-8959, Gupta, Ravindra K, Ioannidis, John P A, Kaleebu, Pontiano, Kantor, Rami; https://orcid.org/0000-0003-3659-1108, Kassaye, Seble G, Kosakovsky Pond, Sergei L, Kouamou, Vinie; https://orcid.org/0000-0003-3531-7780, Kouyos, Roger D, Kuritzkes, Daniel R, Lessells, Richard; https://orcid.org/0000-0003-0926-710X, Marcelin, Anne-Genevieve, Mbuagbaw, Lawrence; https://orcid.org/0000-0001-5855-5461, Minalga, Brian; https://orcid.org/0000-0002-8447-390X, Ndembi, Nicaise, Neher, Richard A, Paredes, Roger; https://orcid.org/0000-0002-6553-691X, Pillay, Deenan; https://orcid.org/0000-0003-2431-244X, et al, Gunthard, Huldrych F, Inzaule, Seth C, Siedner, Mark J; https://orcid.org/0000-0003-3506-842X, Little, Susan J; https://orcid.org/0000-0002-7645-9737, Avila-Rios, Santiago; https://orcid.org/0000-0003-3371-4248, Ayitewala, Alisen, Bosch, Ronald J, Calvez, Vincent, Ceccherini-Silberstein, Francesca, Charpentier, Charlotte; https://orcid.org/0000-0002-6441-7054, Descamps, Diane, Eshleman, Susan H; https://orcid.org/0000-0002-4587-791X, Fokam, Joseph; https://orcid.org/0000-0002-1501-2763, Frenkel, Lisa M; https://orcid.org/0000-0001-9566-8959, Gupta, Ravindra K, Ioannidis, John P A, Kaleebu, Pontiano, Kantor, Rami; https://orcid.org/0000-0003-3659-1108, Kassaye, Seble G, Kosakovsky Pond, Sergei L, Kouamou, Vinie; https://orcid.org/0000-0003-3531-7780, Kouyos, Roger D, Kuritzkes, Daniel R, Lessells, Richard; https://orcid.org/0000-0003-0926-710X, Marcelin, Anne-Genevieve, Mbuagbaw, Lawrence; https://orcid.org/0000-0001-5855-5461, Minalga, Brian; https://orcid.org/0000-0002-8447-390X, Ndembi, Nicaise, Neher, Richard A, Paredes, Roger; https://orcid.org/0000-0002-6553-691X, Pillay, Deenan; https://orcid.org/0000-0003-2431-244X, et al, and Gunthard, Huldrych F
Abstract: • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.
Published: 2023

42. Migrating a Well-Established Longitudinal Cohort Database From Oracle SQL to Research Electronic Data Entry (REDCap): Data Management Research and Design Study

Author: Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Smith, Daniel; https://orcid.org/0009-0002-8283-3227, Scherrer, Alexandra; https://orcid.org/0000-0003-4870-179X, Paioni, Paolo; https://orcid.org/0000-0002-3904-1606, Kohns Vasconcelos, Malte; https://orcid.org/0000-0002-6207-9442, Aebi-Popp, Karoline; https://orcid.org/0000-0002-9337-900X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kahlert, Christian R; https://orcid.org/0000-0002-0784-3276, Swiss HIV Cohort Study and the Swiss Mother and Child HIV Cohort, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Smith, Daniel; https://orcid.org/0009-0002-8283-3227, Scherrer, Alexandra; https://orcid.org/0000-0003-4870-179X, Paioni, Paolo; https://orcid.org/0000-0002-3904-1606, Kohns Vasconcelos, Malte; https://orcid.org/0000-0002-6207-9442, Aebi-Popp, Karoline; https://orcid.org/0000-0002-9337-900X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kahlert, Christian R; https://orcid.org/0000-0002-0784-3276, and Swiss HIV Cohort Study and the Swiss Mother and Child HIV Cohort
Abstract: BACKGROUND: Providing user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. OBJECTIVE: The objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. METHODS: MoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. RESULTS: The key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed "branching logic"). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were
Published: 2023

43. Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial

Author: West, Emily, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Grube, Christina, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Wanner, Katrin, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Hampel, Benjamin, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, West, Emily, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Grube, Christina, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Wanner, Katrin, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Hampel, Benjamin, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, and Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723
Abstract: BACKGROUND: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. RESULTS: Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. CONCLUSIONS: This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy.
Published: 2023

44. Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years

Author: Schoepf, Isabella C, Esteban-Cantos, Andrés, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Rodés, Berta, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Rodríguez-Centeno, Javier, Riebensahm, Carlotta, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Arribas, José R, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Swiss HIV Cohort Study, Schoepf, Isabella C, Esteban-Cantos, Andrés, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Rodés, Berta, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Rodríguez-Centeno, Javier, Riebensahm, Carlotta, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Arribas, José R, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, and Swiss HIV Cohort Study
Abstract: BACKGROUND: Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). We aimed to make a long-term comparison of epigenetic ageing dynamics in people with HIV during untreated HIV infection and during suppressive ART. METHODS: In this longitudinal study, conducted over 17 years in HIV outpatient clinics in Switzerland, we applied 5 established epigenetic age estimators (epigenetic clocks) in peripheral blood mononuclear cells (PBMCs) in Swiss HIV Cohort Study participants before or during suppressive ART. All participants had a longitudinal set of PBMC samples available at four timepoints (T1-T4). T1 and T2 had to be 3 years or longer apart, as did T3 and T4. We assessed epigenetic age acceleration (EAA) and a novel rate of epigenetic ageing. FINDINGS: Between March 13, 1990, and Jan 18, 2018, we recruited 81 people with HIV from the Swiss HIV Cohort Study. We excluded one participant because a sample did not meet quality checks (transmission error). 52 (65%) of 80 patients were men, 76 (95%) were white, and the median patient age was 43 (IQR 37·5-47) years. Per year of untreated HIV infection (median observation 8·08 years, IQR 4·83-11·09), mean EAA was 0·47 years (95% CI 0·37 to 0·57) for Horvath's clock, 0·43 years (0·3 to 0·57) for Hannum's clock, 0·36 years (0·27 to 0·44) for SkinBlood clock, and 0·69 years (0·51 to 0·86) for PhenoAge. Per year of suppressive ART (median observation 9·8 years, IQR 7·2-11), mean EAA was -0·35 years (95% CI -0·44 to -0·27) for Horvath's clock, -0·39 years (-0·50 to -0·27) for Hannum's clock, -0·26 years (-0·33 to -0·18) for SkinBlood clock, and -0·49 years (-0·64 to -0·35) for PhenoAge. Our findings indicate that people with HIV epigenetically aged by a mean of 1·47 years for Horvath's clock, 1·43 years for Hannum's clock, 1·36 years for SkinBlood clock, and 1·69 years for PhenoAge per year of untreated HIV infection; and 0·65 years for Horvath's cl
Published: 2023

45. Understanding the decline of incident, active tuberculosis in people with HIV in Switzerland

Author: Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Reiber, Claudine, Kälin, Marisa, Bartl, Lena, Notter, Julia, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Nemeth, Johannes; https://orcid.org/0000-0003-0683-456X, Swiss HIV Cohort Study, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Reiber, Claudine, Kälin, Marisa, Bartl, Lena, Notter, Julia, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Nemeth, Johannes; https://orcid.org/0000-0003-0683-456X, and Swiss HIV Cohort Study
Abstract: BACKGROUND: People with human immunodeficiency virus type 1 (HIV) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. METHODS: We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. RESULTS: In 21,528 PWH, LTBI prevalence declined from 15.1% in 2001 to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (HR 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. CONCLUSIONS: TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.
Published: 2023

46. Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

Author: Jaha, Bashkim, Schenkel, Corinne D, Jörimann, Lisa, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leemann, Christine, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Swiss HIV Cohort Study, Jaha, Bashkim, Schenkel, Corinne D, Jörimann, Lisa, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leemann, Christine, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, and Swiss HIV Cohort Study
Abstract: BACKGROUND: Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA. OBJECTIVES: A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia. METHODS: Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs). RESULTS: Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs. CONCLUSIONS: We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.
Published: 2023

47. Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study

Author: Avery, Emma F, Kleynhans, Julia N, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Schoepf, Isabella C, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kootstra, Neeltje A, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Ryom, Lene, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Swiss HIV Cohort Study, Avery, Emma F, Kleynhans, Julia N, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Schoepf, Isabella C, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kootstra, Neeltje A, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Ryom, Lene, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, and Swiss HIV Cohort Study
Abstract: BACKGROUND: People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS: We included 536 cases with a first CAD event (2000-2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300-7995] vs 5900 [4910-7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. CONCLUSIONS: PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.
Published: 2023

48. Sex and gender in infection and immunity: addressing the bottlenecks from basic science to public health and clinical applications

Author: Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Consiglio, Camila R; https://orcid.org/0000-0002-8901-2328, Huisman, Jana S; https://orcid.org/0000-0002-1782-8109, de Lange, Ann-Marie G; https://orcid.org/0000-0002-5150-6656, Peckham, Hannah; https://orcid.org/0000-0002-9668-4683, Vallejo-Yagüe, Enriqueta; https://orcid.org/0000-0002-5911-2037, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Islander, Ulrika; https://orcid.org/0000-0002-8493-1739, Neuner-Jehle, Nadia, Pujantell, Maria; https://orcid.org/0000-0002-9471-5853, Roth, Olivia; https://orcid.org/0000-0002-7349-7797, Schirmer, Melanie; https://orcid.org/0000-0001-6456-3679, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Hachfeld, Anna; https://orcid.org/0000-0001-9308-7130, Aebi-Popp, Karoline; https://orcid.org/0000-0002-9337-900X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Bonhoeffer, Sebastian; https://orcid.org/0000-0001-8052-3925, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Consiglio, Camila R; https://orcid.org/0000-0002-8901-2328, Huisman, Jana S; https://orcid.org/0000-0002-1782-8109, de Lange, Ann-Marie G; https://orcid.org/0000-0002-5150-6656, Peckham, Hannah; https://orcid.org/0000-0002-9668-4683, Vallejo-Yagüe, Enriqueta; https://orcid.org/0000-0002-5911-2037, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Islander, Ulrika; https://orcid.org/0000-0002-8493-1739, Neuner-Jehle, Nadia, Pujantell, Maria; https://orcid.org/0000-0002-9471-5853, Roth, Olivia; https://orcid.org/0000-0002-7349-7797, Schirmer, Melanie; https://orcid.org/0000-0001-6456-3679, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Hachfeld, Anna; https://orcid.org/0000-0001-9308-7130, Aebi-Popp, Karoline; https://orcid.org/0000-0002-9337-900X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Bonhoeffer, Sebastian; https://orcid.org/0000-0001-8052-3925
Abstract: Although sex and gender are recognized as major determinants of health and immunity, their role is rarely considered in clinical practice and public health. We identified six bottlenecks preventing the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine and public health policies. (i) A terminology-related bottleneck, linked to the definitions of sex and gender themselves, and the lack of consensus on how to evaluate gender. (ii) A data-related bottleneck, due to gaps in sex-disaggregated data, data on trans/non-binary people and gender identity. (iii) A translational bottleneck, limited by animal models and the underrepresentation of gender minorities in biomedical studies. (iv) A statistical bottleneck, with inappropriate statistical analyses and results interpretation. (v) An ethical bottleneck posed by the underrepresentation of pregnant people and gender minorities in clinical studies. (vi) A structural bottleneck, as systemic bias and discriminations affect not only academic research but also decision makers. We specify guidelines for researchers, scientific journals, funding agencies and academic institutions to address these bottlenecks. Following such guidelines will support the development of more efficient and equitable care strategies for all.
Published: 2023

49. Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity

Author: Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Epp, Selina, Mohloanyane, Tsepang; https://orcid.org/0000-0002-8530-1499, Nsakala, Bienvenu L, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Epp, Selina, Mohloanyane, Tsepang; https://orcid.org/0000-0002-8530-1499, Nsakala, Bienvenu L, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723
Abstract: BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV). METHODS: Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2 and between older age or obesity and the immunoglobulin G response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.
Published: 2023

50. Mortality and morbidity related to hepatitis C virus infection in hospitalized adults-A propensity score matched analysis

Author: Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Beeler, Patrick E; https://orcid.org/0000-0002-6097-2480, Müllhaupt, Beat; https://orcid.org/0000-0002-9020-8192, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Maeschli, Bettina, Bruggmann, Philip, Fehr, Jan S; https://orcid.org/0000-0003-1113-9895, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Beeler, Patrick E; https://orcid.org/0000-0002-6097-2480, Müllhaupt, Beat; https://orcid.org/0000-0002-9020-8192, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Maeschli, Bettina, Bruggmann, Philip, Fehr, Jan S; https://orcid.org/0000-0003-1113-9895, and Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348
Abstract: The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic phenotyping strategies on routinely collected data from patients hospitalized at a tertiary referral hospital in Switzerland between 2009 and 2017. Individuals with HCV infection were identified using International Classification of Disease (ICD)-10 codes, prescribed medications and laboratory results (antibody, PCR, antigen or genotype test). Controls were selected using propensity score methods (matching by age, sex, intravenous drug use, alcohol abuse and HIV co-infection). Main outcomes were in-hospital mortality and attributable mortality (in HCV cases and study population). The non-matched dataset included records from 165,972 individuals (287,255 hospital stays). Electronic phenotyping identified 2285 stays with evidence of HCV infection (1677 individuals). Propensity score matching yielded 6855 stays (2285 with HCV, 4570 controls). In-hospital mortality was higher in HCV cases (RR 2.10, 95%CI 1.64 to 2.70). Among those infected, 52.5% of the deaths were attributable to HCV (95%CI 38.9 to 63.1). When cases were matched, the fraction of deaths attributable to HCV was 26.9% (HCV prevalence: 33%), whilst in the non-matched dataset, it was 0.92% (HCV prevalence: 0.8%). In this study, HCV infection was strongly associated with increased mortality. Our methodology may be used to monitor the efforts towards meeting the WHO elimination targets and underline the importance of electronic cohorts as a basis for national longitudinal surveillance.
Published: 2023

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