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1. Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods

Author

Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Jackson-Perry, D., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Labhardt, N., Leuzinger, K., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Notter, J., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Salazar-Vizcaya, L., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Weisser, M., Yerly, S., Otte, Fabian, Zhang, Yuepeng, Spagnuolo, Julian, Thielen, Alexander, Däumer, Martin, Wiethe, Carsten, Stoeckle, Marcel, Kusejko, Katharina, Klein, Florian, Metzner, Karin J., and Klimkait, Thomas

Published
2023
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2. HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Author

Zhang, Yuepeng, Otte, Fabian, Stoeckle, Marcel, Thielen, Alexander, Däumer, Martin, Kaiser, Rolf, Kusejko, Katharina, Metzner, Karin J., and Klimkait, Thomas

Subjects
VIRAL genomes, VIRAL envelopes, GENETIC variation, IMMUNITY, CD4 lymphocyte count
Abstract

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants. The single dominating variants were more often found in individuals starting ART during early infection phases, indicating that early treatment might limit reservoir diversification. At the same time, more sequence-diverse HIV reservoirs correlated with a poorer immune status, indicated by lower CD4 count, a higher number of regimen changes and more co-morbidities. Furthermore, we noted that in T-cell populations in the peripheral blood, replication-competent HIV-1 is predominantly present in Lymph node homing TN (naïve) and TCM (central memory) T cells. Provirus genomes archived in TTM (transitional memory) and TEM (effector memory) T cells more frequently tended to carry inactivating mutations and, population-wise, possess changes in the genetic diversity. These discriminating properties of the viral reservoir in T-cell subsets may have important implications for new early therapy strategies, underscoring the critical role of early therapy in preserving robust immune surveillance and constraining the viral reservoir. Author summary: Our study demonstrates that a poor immune status associates with and may form a basis for HIV reservoir diversification. Reservoirs for replication-competent, infectious viruses are mainly found in TN and TCM, which harbor a small number of intact viral variants. A distinct population of archived HIV sequences, residing in TTM and TEM, is characterized by a shifted genetic diversity. While the former cells are likely to harbor a promptly re-activatable latent reservoir, the latter with often defective but more variable viral genomes could thus represent a source for retroviral recombination and reactivation. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Therapeutic Drug Monitoring of Long-Acting Rilpivirine and Cabotegravir for Treatment of HIV-1 Infection—A Case Series of Five Patients With One Virologic Failure After Development of Two-Class Resistance.

Author

Gerstenberg, Jacob, Klinker, Hartwig, Baier, Michael, Braun, Amrei von, Seybold, Ulrich, Helbig, Carlotta, Däumer, Martin, Korn, Klaus, Stephan, Christoph, and Schleenvoigt, Benjamin T

Subjects
DRUG monitoring, HIV
Abstract

Virologic failure of long-acting rilpivirine/cabotegravir is rare but may result in severely limited treatment options. Known risk factors cannot predict all cases. Therapeutic drug monitoring (TDM) may help identify patients at risk, but reliable thresholds are missing. We report retrospective TDM in a cohort of 5 patients, including 1 virological failure. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Simultaneous analysis of seven 16S rRNA hypervariable gene regions increases efficiency in marine bacterial diversity detection.

Author

Leontidou, Kleopatra, Abad‐Recio, Ion L., Rubel, Verena, Filker, Sabine, Däumer, Martin, Thielen, Alexander, Lanzén, Anders, and Stoeck, Thorsten

Subjects
HYPERVARIABLE regions, BACTERIAL diversity, RIBOSOMAL RNA, SHOTGUN sequencing, MARINE biodiversity, BACTERIAL communities, DNA sequencing, SEDIMENT sampling
Abstract

Environmental DNA sequencing is the gold standard to reveal microbial community structures. In most applications, a one‐fragment PCR approach is applied to amplify a taxonomic marker gene, usually a hypervariable region of the 16S rRNA gene. We used a new reverse complement (RC)‐PCR‐based assay that amplifies seven out of the nine hypervariable regions of the 16S rRNA gene, to interrogate bacterial communities in sediment samples collected from different coastal marine sites with an impact gradient. In parallel, we employed a traditional one‐fragment analysis of the hypervariable V3–V4 region to investigate whether the RC‐PCR reveals more of the 'unseen' diversity obtained by the one‐fragment approach. As a benchmark for the full deck of diversity, we subjected the samples to PCR‐free metagenomic sequencing. None of the two PCR‐based approaches recorded the full taxonomic repertoire obtained from the metagenomics datasets. However, the RC‐PCR approach detected 2.8 times more bacterial genera compared to the near‐saturation sequenced V3–V4 samples. RC‐PCR is an ideal compromise between the standard one‐fragment approach and metagenomics sequencing and may guide future environmental sequencing studies, in which bacterial diversity is a central subject. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods

Author

Otte, Fabian, primary, Zhang, Yuepeng, additional, Spagnuolo, Julian, additional, Thielen, Alexander, additional, Däumer, Martin, additional, Wiethe, Carsten, additional, Stoeckle, Marcel, additional, Kusejko, Katharina, additional, Klein, Florian, additional, Metzner, Karin J., additional, Klimkait, Thomas, additional, Abela, I., additional, Aebi-Popp, K., additional, Anagnostopoulos, A., additional, Battegay, M., additional, Bernasconi, E., additional, Braun, D.L., additional, Bucher, H.C., additional, Calmy, A., additional, Cavassini, M., additional, Ciuffi, A., additional, Dollenmaier, G., additional, Egger, M., additional, Elzi, L., additional, Fehr, J., additional, Fellay, J., additional, Furrer, H., additional, Fux, C.A., additional, Günthard, H.F., additional, Hachfeld, A., additional, Haerry, D., additional, Hasse, B., additional, Hirsch, H.H., additional, Hoffmann, M., additional, Hösli, I., additional, Huber, M., additional, Jackson-Perry, D., additional, Kahlert, C.R., additional, Kaiser, L., additional, Keiser, O., additional, Klimkait, T., additional, Kouyos, R.D., additional, Kovari, H., additional, Kusejko, K., additional, Labhardt, N., additional, Leuzinger, K., additional, Martinez de Tejada, B., additional, Marzolini, C., additional, Metzner, K.J., additional, Müller, N., additional, Nemeth, J., additional, Nicca, D., additional, Notter, J., additional, Paioni, P., additional, Pantaleo, G., additional, Perreau, M., additional, Rauch, A., additional, Salazar-Vizcaya, L., additional, Schmid, P., additional, Speck, R., additional, Stöckle, M., additional, Tarr, P., additional, Trkola, A., additional, Wandeler, G., additional, Weisser, M., additional, and Yerly, S., additional

Published
2023
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9. Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods

Author

Otte, Fabian, Zhang, Yuepeng, Spagnuolo, Julian, Thielen, Alexander, Däumer, Martin, Wiethe, Carsten, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Klein, Florian, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Swiss HIV Cohort Study, Otte, Fabian, Zhang, Yuepeng, Spagnuolo, Julian, Thielen, Alexander, Däumer, Martin, Wiethe, Carsten, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Klein, Florian, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, and Swiss HIV Cohort Study

Abstract

While combination therapy completely suppresses HIV-1 replication in blood, functional virus persists in CD4$^{+}$ T cell subsets in non-peripheral compartments that are not easily accessible. To fill this gap, we investigated tissue-homing properties of cells that transiently appear in the circulating blood. Through cell separation and in vitro stimulation, the HIV-1 "Gag and Envelope reactivation co-detection assay" (GERDA) enables sensitive detection of Gag+/Env+ protein-expressing cells down to about one cell per million using flow cytometry. By associating GERDA with proviral DNA and polyA-RNA transcripts, we corroborate the presence and functionality of HIV-1 in critical body compartments utilizing t-distributed stochastic neighbor embedding (tSNE) and density-based spatial clustering of applications with noise (DBSCAN) clustering with low viral activity in circulating cells early after diagnosis. We demonstrate transcriptional HIV-1 reactivation at any time, potentially giving rise to intact, infectious particles. With single-cell level resolution, GERDA attributes virus production to lymph-node-homing cells with central memory T cells (T$_{CM}$s) as main players, critical for HIV-1 reservoir eradication.

Published
2023

11. Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 Omicron-Infected Immunocompromised Patients

Author

Gliga, Smaranda, primary, Lübke, Nadine, additional, Killer, Alexander, additional, Gruell, Henning, additional, Walker, Andreas, additional, Dilthey, Alexander T, additional, Thielen, Alexander, additional, Lohr, Carolin, additional, Flaßhove, Charlotte, additional, Krieg, Sarah, additional, Pereira, Joanna Ventura, additional, Seraphin, Tobias Paul, additional, Zaufel, Alex, additional, Däumer, Martin, additional, Orth, Hans-Martin, additional, Feldt, Torsten, additional, Bode, Johannes G, additional, Klein, Florian, additional, Timm, Jörg, additional, Luedde, Tom, additional, and Jensen, Björn-Erik Ole, additional

Published
2022
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12. An international multicenter study on HIV-1 drug resistance testing by 454 ultra-deep pyrosequencing

Author

Simen, Birgitte B., Braverman, Michael S., Abbate, Isabella, Aerssens, Jeroen, Bidet, Yannick, Bouchez, Olivier, Gabriel, Christian, Izopet, Jacques, Kessler, Harald H., Stelzl, Evelyn, Di Giallonardo, Francesca, Schlapbach, Ralph, Radonic, Aleksander, Paredes, Roger, Recordon-Pinson, Patricia, Sakwa, James, St. John, Elizabeth P., Schmitz-Agheguian, Gudrun G., Metzner, Karin J., and Däumer, Martin P.

Published
2014
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13. Arevir: A Secure Platform for Designing Personalized Antiretroviral Therapies Against HIV

Author

Roomp, Kirsten, Beerenwinkel, Niko, Sing, Tobias, Schülter, Eugen, Büch, Joachim, Sierra-Aragon, Saleta, Däumer, Martin, Hoffmann, Daniel, Kaiser, Rolf, Lengauer, Thomas, Selbig, Joachim, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Istrail, Sorin, editor, Pevzner, Pavel, editor, Waterman, Michael, editor, Leser, Ulf, editor, Naumann, Felix, editor, and Eckman, Barbara, editor

Published
2006
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14. Characterization of Novel HIV Drug Resistance Mutations Using Clustering, Multidimensional Scaling and SVM-Based Feature Ranking

Author

Sing, Tobias, Svicher, Valentina, Beerenwinkel, Niko, Ceccherini-Silberstein, Francesca, Däumer, Martin, Kaiser, Rolf, Walter, Hauke, Korn, Klaus, Hoffmann, Daniel, Oette, Mark, Rockstroh, Jürgen K., Fätkenheuer, Gert, Perno, Carlo-Federico, Lengauer, Thomas, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Carbonell, Jaime G., editor, Siekmann, Jörg, editor, Jorge, Alípio Mário, editor, Torgo, Luís, editor, Brazdil, Pavel, editor, Camacho, Rui, editor, and Gama, João, editor

Published
2005
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20. Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 Omicron-Infected Immunocompromised Patients.

Author

Gliga, Smaranda, Lübke, Nadine, Killer, Alexander, Gruell, Henning, Walker, Andreas, Dilthey, Alexander T, Thielen, Alexander, Lohr, Carolin, Flaßhove, Charlotte, Krieg, Sarah, Pereira, Joanna Ventura, Seraphin, Tobias Paul, Zaufel, Alex, Däumer, Martin, Orth, Hans-Martin, Feldt, Torsten, Bode, Johannes G, Klein, Florian, Timm, Jörg, and Luedde, Tom

Subjects
COVID-19, ACADEMIC medical centers, IMMUNOCOMPROMISED patients, DESCRIPTIVE statistics, RESEARCH funding, LONGITUDINAL method
Abstract

Background Monoclonal antibodies (mAbs) that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding, resulting in an increased risk of viral escape. Methods In an observational, prospective cohort, 57 patients infected with Omicron variants who received sotrovimab alone or in combination with remdesivir were followed. The study end points were a decrease in SARS-CoV-2 RNA <106 copies/mL in nasopharyngeal swabs at day 21 and the emergence of escape mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed using whole-genome sequencing. Individual variants within the quasispecies were subsequently quantified and further characterized using a pseudovirus neutralization assay. Results The majority of patients (43 of 57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. Infections by Omicron/BA.1 comprised 82.5%, while 17.5% were infected by Omicron/BA.2. Twenty-one days after sotrovimab administration, 12 of 43 (27.9%) immunodeficient patients had prolonged viral shedding compared with 1 of 14 (7.1%) immunocompetent patients (P =.011). Viral spike protein mutations, some specific for Omicron (e.g. P337S and/or E340D/V), emerged in 14 of 43 (32.6%) immunodeficient patients, substantially reducing sensitivity to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced emergence of escape variants. Conclusions Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need for dedicated clinical trials in this patient population. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Single oral doses of MK-8507, a novel non-nucleoside reverse transcriptase inhibitor, suppress HIV-1 RNA for a week

Author

Schürmann, Dirk, primary, Rudd, Deanne Jackson, additional, Schaeffer, Andrea, additional, De Lepeleire, Inge, additional, Friedman, Evan J., additional, Robberechts, Martine, additional, Zhang, Saijuan, additional, Liu, Yang, additional, Kandala, Bhargava, additional, Keicher, Christian, additional, Däumer, Martin, additional, Hofmann, Jörg, additional, Grobler, Jay A., additional, Stoch, S. Aubrey, additional, Iwamoto, Marian, additional, and Ankrom, Wendy, additional

Published
2021
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22. Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case–control study using centralized ultrasensitive 454 pyrosequencing

Author

Cozzi-Lepri, Alessandro, Noguera-Julian, Marc, Di Giallonardo, Francesca, Schuurman, Rob, Däumer, Martin, Aitken, Sue, Ceccherini-Silberstein, Francesca, DʼArminio Monforte, Antonella, Geretti, Anna Maria, Booth, Clare L., Kaiser, Rolf, Michalik, Claudia, Jansen, Klaus, Masquelier, Bernard, Bellecave, Pantxika, Kouyos, Roger D., Castro, Erika, Furrer, Hansjakob, Schultze, Anna, Günthard, Huldrych F., Brun-Vezinet, Francoise, Paredes, Roger, Metzner, Karin J., Paredes, Roger, Metzner, Karin J., Cozzi-Lepri, Alessandro, Schuurman, Rob, Brun-Vezinet, Francoise, Günthard, Huldrych, Ceccherini-Silberstein, Francesca, Kaiser, Rolf, Geretti, Anna Maria, Brockmeyer, Norbert, Masquelier, Bernard, Dabis, F., Bruyand, M., Chêne, G., Dabis, F., Lawson-Ayayi, S., Thiébaut, R., Wittkop, L., André, K., Bonnal, F., Bonnet, F., Bernard, N., Caunègre, L., Cazanave, C., Ceccaldi, J., Chossat, I., Courtaud, K., Dauchy, F. A., De Witte, S., Dupon, M., Dupont, A., Duffau, P., Dutronc, H., Farbos, S., Gaborieau, V., Gemain, M. C., Gerard, Y., Greib, C., Hessamfar, M., Lacoste, D., Lataste, P., Lazaro, E., Longy-Boursier, M., Malvy, D., Meraud, J. P., Mercié, P., Monlun, E., Morlat, P., Neau, D., Ochoa, A., Pellegrin, J. L., Pistone, T., Receveur, M. C., Schmeltz, J. Roger, Tchamgoué, S., Vandenhende, M. A., Vareil, M.O., Viallard, J. F., Moreau, J. F., Pellegrin, I., Fleury, H., Lafon, M. E., Masquelier, B., Reigadas, S., Trimoulet, P., Bouchet, S., Breilh, D., Molimard, M., Titier, K., Haramburu, F., Miremont-Salamé., G., Blaizeau, M. J., Decoin, M., Delaune, J., Delveaux, S., DʼIvernois, C., Hanapier, C., Leleux, O., Lenaud, E., Uwamaliya-Nziyumvira, B., Sicard, X., Geffard, S., Le Marec, F., Conte, V., Frosch, A., Leray, J., Palmer, G., Touchard, D., Bonnet, F., Breilh, D., Chêne, G., Dabis, F., Dupon, M., Fleury, H., Malvy, D., Mercié, P., Morlat, P., Neau, D., Pellegrin, I., Pellegrin, J. L., Bouchet, S., Gaborieau, V., Lacoste, D., Tchamgoué, S., Thiébaut, R., Losso, M., Kundro, M., Ramos Mejia, J. M., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Nielsen, J., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A.-B. E., Skinhøj, P., Pedersen, C., Ostergaard, L., Dragsted, U. B., Nielsen, L. N., Zilmer, K., Smidt, Jelena, Ristola, M., Katlama, C., Viard, J. P., Girard, P. M., Vanhems, P., Pradier, C., Dabis, F., Neau, D., Duvivier, C., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Bickel, M., Bogner, J., Fätkenheuer, G., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Sambatakou, H., Banhegyi, D., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., HassounRambam, G., Elinav, H., HaouziHadassah, M., EspositoI, R., Mazzotta, F., Vullo, V., Moroni, M., Andreoni, M., Angarano, G., Antinori, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Monforte, A. DʼArminio, Antinori, A., Castagna, A., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Andreoni, M., Ammassari, A., Antinori, A., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, M. R., Castagna, A., Ceccherini-Silberstein, F., Cingolani, A., Cinque, P., Cozzi-Lepri, A., De Luca, A., Di Biagio, A., Girardi, E., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Lo Caputo, S., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Mussini, C., Puoti, M., Quiros Roldan, E., Rusconi, S., Cozzi-Lepri, A., Cicconi, P., Fanti, I., Formenti, T., Galli, L., Lorenzini, P., Carletti, F., Carrara, S., Castrogiovanni, A., Di Caro, A., Petrone, F., Prota, G., Quartu, S., Giacometti, A., Costantini, A., Mazzoccato, S., Angarano, G., Monno, L., Santoro, C., Maggiolo, F., Suardi, C., Viale, P., Vanino, E., Verucchi, G., Castelli, F., Quiros Roldan, E., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Lo Caputo, S., Cassola, G., Viscoli, C., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Bonfanti, P., Caramma, I., Chiodera, A., Castelli, A. P., Galli, M., Lazzarin, A., Rizzardini, G., Puoti, M., DʼArminio Monforte, A., Ridolfo, A. L., Piolini, R., Castagna, A., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Marchetti, G., Mussini, C., Puzzolante, C., Gori, A., Lapadula, G., Abrescia, N., Chirianni, A., Guida, M. G., Gargiulo, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Cauda, R., Andreoni, M., Antinori, A., Vullo, V., Cingolani, A., dʼAvino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Sasset, L., Mura, M. S., Madeddu, G., De Luca, A., Rossetti, B., Caramello, P., Di Perri, G., Orofino, G. C., Bonora, S., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Brockmeyer, N. H., Skaletz-Rorowski, A., Dupke, S., Baumgarten, A., Carganico, A., Köppe, S., Kreckel, P., Lauenroth-Mai, E., Freiwald-Rausch, M., Gölz, J., Moll, A., Zeitz, M., Hower, M., Reuter, S., Jensen, B., Harrer, T., Esser, S., Brodt, H. R., Plettenberg, A., Stöhr, A., Buhk, T., Stellbrink, H. J., Stoll, M., Schmidt, R., Kuhlmann, B., Mosthaf, F. A., Rieke, A., Becker, W., Volkert, R., Jäger, H., Hartl, H., Mutz, A., Ulmer, A., Müller, M., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C. A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.

Published
2015
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25. Full-length haplotype reconstruction to infer the structure of heterogeneous virus populations

Author

Giallonardo, Francesca Di, Töpfer, Armin, Rey, Melanie, Prabhakaran, Sandhya, Duport, Yannick, Leemann, Christine, Schmutz, Stefan, Campbell, Nottania K., Joos, Beda, Lecca, Maria Rita, Patrignani, Andrea, Däumer, Martin, Beisel, Christian, Rusert, Peter, Trkola, Alexandra, Günthard, Huldrych F., Roth, Volker, Beerenwinkel, Niko, and Metzner, Karin J.

Published
2014
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29. Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Clusters Based on Integrated Genomic Surveillance, Outbreak Analysis and Contact Tracing in an Urban Setting.

Author

Walker, Andreas, Houwaart, Torsten, Finzer, Patrick, Ehlkes, Lutz, Tyshaieva, Alona, Damagnez, Maximilian, Strelow, Daniel, Duplessis, Ashley, Nicolai, Jessica, Wienemann, Tobias, Tamayo, Teresa, Vasconcelos, Malte Kohns, Hülse, Lisanna, Hoffmann, Katrin, Lübke, Nadine, Hauka, Sandra, Andree, Marcel, Däumer, Martin P, Thielen, Alexander, and Kolbe-Busch, Susanne

Subjects
PUBLIC health surveillance, COVID-19, SEQUENCE analysis, INFORMATION storage & retrieval systems, MEDICAL databases, PUBLIC health, GENETIC testing, GENOMICS, INFECTIOUS disease transmission, INTERPROFESSIONAL relations, CLINICAL medicine, CONTACT tracing, COVID-19 pandemic
Abstract

Background Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. Methods In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. Results Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. Conclusions Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mattia C. F., Mackie, Nicola, Di Giambenedetto, Simona, Zazzi, Maurizio, Camacho, Ricardo, Fanti, Iuri, Torti, Carlo, Sönnerborg, Anders, Kaiser, Rolf, Codoñer, Francisco M., Van Laethem, Kristel, Bansi, Loveleen, van de Vijver, David A. M. C., Geretti, Anna Maria, De Luca, Andrea, Giacometti, Andrea, Butini, Luca, del Gobbo, Romana, Menzo, Stefano, Tacconi, Danilo, Corbelli, Giovanni, Zanussi, Stefania, Monno, Laura, Punzi, Grazia, Maggiolo, Franco, Callegaro, Annapaola, Calza, Leonardo, Carla Re, Maria, Pristerà, Raffaele, Turconi, Paola, Mandas, Antonella, Tini, Sauro, Zoncada, Alessia, Paolini, Elisabetta, Amadio, Giorgio, Sighinolfi, Laura, Zuccati, Giuliano, Morfini, Massimo, Manetti, Roberto, Corsi, Paola, Galli, Luisa, Di Pietro, Massimo, Bartalesi, Filippo, Colao, Grazia, Tosti, Andrea, Di Biagio, Antonio, Setti, Maurizio, Bruzzone, Bianca, Penco, Giovanni, Trezzi, Michele, Orani, Anna, Pardelli, Riccardo, De Gennaro, Michele, Chiodera, Alessandro, Scalzini, Alfredo, Palvarini, Loredana, Almi, Paolo, Todaro, Giovanni, dʼArminio Monforte, Antonella, Cicconi, Paola, Rusconi, Stefano, Gismondo, Maria Rita, Gismondo, Maria Rita, Micheli, Valeria, Biondi, Maria Luisa, Gianotti, Nicola, Capetti, Amedeo, Meraviglia, Paola, Boeri, Enzo, Mussini, Cristina, Pecorari, Monica, Soria, Alessandro, Vecchi, Laura, Santirocchi, Maurizio, Brustia, Diego, Ravanini, Paolo, Bello, Federico Dal, Romano, Nino, Mancuso, Salvatrice, Calzetti, Carlo, Maserati, Renato, Filice, Gaetano, Baldanti, Fausto, Francisci, Daniela, Parruti, Giustino, Polilli, Ennio, Sacchini, Daria, Martinelli, Chiara, Consolini, Rita, Vatteroni, Linda, Vivarelli, Angela, Dionisio, Daniele, Nerli, Alessandro, Lenzi, Lucia, Magnani, Giacomo, Ortolani, Patrizia, Andreoni, Massimo, Palamara, Guido, Fimiani, Caterina, Palmisano, Lucia, De Luca, Andrea, Fadda, Giovanni, Vullo, Vincenzo, Turriziani, Ombretta, Montano, Marco, Cenderello, Giovanni, Gonnelli, Angela, Zazzi, Maurizio, Palumbo, Michele, Ghisetti, Valeria, Bonora, Stefano, Foglie, Palma Delle, Rossi, Cristina, Grossi, Paolo, Seminari, Elena, Poletti, Federica, Mondino, Vincenzo, Malena, Marina, Lattuada, Emanuela, Lengauer, Thomas, Däumer, Martin, Hoffmann, Daniel, Kaiser, Rolf, Schülter, Eugen, Müller, Claudia, Oette, Mark, Reuter, Stefan, Esser, Stefan, Fätkenheuer, Gerd, Rockstroh, Jürgen, van de Vijver, David AMC, Incardona, Francesca, Rosen-Zvi, Michal, Lengauer, Thomas, Camacho, Ricardo, Clotet, Bonaventura, Thalme, Anders, Svedhem, Veronica, Bratt, Göran, Gargiulo, Franco, Lapadula, Giuseppe, Manca, Nino, Paraninfo, Giuseppe, Quiros-Roldan, Eugenia, Carosi, Giampiero, Castelnuovo, Filippo, Vandamme, Anne-Mieke, Van Laethem, Kristel, Van Wijngaerden, Eric, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Dunn, David, Easterbrook, Philippa, Fisher, Martin, Gazzard, Brian, Garrett, Nigel, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Leen, Clifford, Orkin, Chloe, Phillips, Andrew, Pillay, Deenan, Porter, Kholoud, Post, Frank, Sabin, Caroline, Sadiq, Tariq, Schwenk, Achim, Walsh, John, Delpech, Valerie, Palfreeman, Adrian, Dunn, David, Glabay, Adam, Porter, Kholoud, Bansi, Loveleen, Hill, Teresa, Phillips, Andrew, Sabin, Caroline, Orkin, Chloe, Garrett, Nigel, Lynch, Janet, Hand, James, de Souza, Carl, Fisher, Martin, Perry, Nicky, Tilbury, Stuart, Churchill, Duncan, Gazzard, Brian, Nelson, Mark, Waxman, Matthew, Mandalia, Sundhiya, Delpech, Valerie, Anderson, Jane, Kall, Meaghan, Post, Frank, Korat, Hardik, Taylor, Chris, Ibrahim, Fowzia, Campbell, Lucy, Easterbrook, Philippa, Babiker, Abdel, Dunn, David, Glabay, Adam, Porter, Kholoud, Gilson, Richard, James, Laura, Brima, Nataliya, Williams, Ian, Schwenk, Achim, Johnson, Margaret, Youle, Mike, Lampe, Fiona, Smith, Colette, Grabowska, Helen, Chaloner, Clinton, Puradiredja, Dewi Ismajani, Bansi, Loveleen, Hill, Teresa, Phillips, Andrew, Sabin, Caroline, Walsh, John, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Leen, Clifford, Wilson, Alan, Gompels, Mark, Dooley, Debbie, Palfreeman, Adrian, Anderson, Jane, Asboe, David, Pozniak, Anton, Cameron, Sheila, Cane, Patricia, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Pillay, Deenan, Lazarus, Linda, Dunn, David, Dolling, David, Fearnhill, Esther, Castro, Hannah, Porter, Kholoud, Coughlin, Kate, Dolling, David, Zuckerman, Mark, Anna Maria, Geretti, Booth, Clare, Goldberg, David, Gompels, Mark, Hale, Antony, Kaye, Steve, Kellam, Paul, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Pillay, Deenan, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zhang, Hongyi, Clark, Duncan, Ushiro-Lumb, Ines, Oliver, Tony, Bibby, David, Mitchell, Suzanne, Smit, Erasmus, Mbisa, Tamyo, Wildfire, Adrian, Tandy, Richard, Shepherd, Jill, Chadwick, David, MacLean, Alasdair, Tong, William, Bennett, Diane, Hopkins, Mark, Tilston, Peter, Booth, Clare, Garcia-Diaz, Ana, Kaye, Steve, and Kirk, Stuart

Published
2011
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32. High turnaround times and low viral resuppression rates after reinforced adherence counselling following a confirmed virological failure diagnostic algorithm in HIV‐infected patients on first‐line antiretroviral therapy from Tanzania

Author

Kroidl, Arne, primary, Burger, Tassilo, additional, Urio, Agatha, additional, Mugeniwalwo, Roki, additional, Mgaya, Jimson, additional, Mlagalila, Faith, additional, Hoelscher, Michael, additional, Däumer, Martin, additional, Salehe, Omar, additional, Sangare, Anthony, additional, Lennemann, Tessa, additional, and Maganga, Lucas, additional

Published
2020
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35. Evolution of raltegravir resistance during therapy

Author

Sichtig, Nadine, Sierra, Saleta, Kaiser, Rolf, Däumer, Martin, Reuter, Stefan, Schülter, Eugen, Altmann, Andre, Fätkenheuer, Gerd, Dittmer, Ulf, Pfister, Herbert, and Esser, Stefan

Published
2009

36. Characterization of Novel HIV Drug Resistance Mutations Using Clustering, Multidimensional Scaling and SVM-Based Feature Ranking

Author

Sing, Tobias, primary, Svicher, Valentina, additional, Beerenwinkel, Niko, additional, Ceccherini-Silberstein, Francesca, additional, Däumer, Martin, additional, Kaiser, Rolf, additional, Walter, Hauke, additional, Korn, Klaus, additional, Hoffmann, Daniel, additional, Oette, Mark, additional, Rockstroh, Jürgen K., additional, Fätkenheuer, Gert, additional, Perno, Carlo-Federico, additional, and Lengauer, Thomas, additional

Published
2005
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38. Trends of prevalence of primary HIV drug resistance in Germany

Author

Sagir, Abdurrahman, Oette, Mark, Kaiser, Rolf, Däumer, Martin, Fätkenheuer, Gerd, Rockstroh, Jürgen Kurt, Knechten, Heribert, Schmutz, Günther, Hower, Martin, Emmelkamp, Jetske, Pfister, Herbert, and Häussinger, Dieter

Published
2007

41. Rapid Rebound of a Preexisting CXCR4-tropic Human Immunodeficiency Virus Variant After Allogeneic Transplantation With CCR5 Δ32 Homozygous Stem Cells

Author

Verheyen, Jens, Thielen, Alexander, Lübke, Nadine, Dirks, Miriam, Widera, Marek, Dittmer, Ulf, Kordelas, Lambros, Däumer, Martin, De Jong, Dorien C.M., Wensing, Annemarie M.J., Kaiser, Rolf, Nijhuis, Monique, Esser, Stefan, Verheyen, Jens, Thielen, Alexander, Lübke, Nadine, Dirks, Miriam, Widera, Marek, Dittmer, Ulf, Kordelas, Lambros, Däumer, Martin, De Jong, Dorien C.M., Wensing, Annemarie M.J., Kaiser, Rolf, Nijhuis, Monique, and Esser, Stefan

Published
2019

44. Failure of Dolutegravir First-Line ART with Selection of Virus Carrying R263K and G118R

Author

Lübke, Nadine, primary, Jensen, Björn, additional, Hüttig, Falk, additional, Feldt, Torsten, additional, Walker, Andreas, additional, Thielen, Alexander, additional, Däumer, Martin, additional, Obermeier, Martin, additional, Kaiser, Rolf, additional, Knops, Elena, additional, Heger, Eva, additional, Sierra, Saleta, additional, Oette, Mark, additional, Lengauer, Thomas, additional, Timm, Jörg, additional, and Häussinger, Dieter, additional

Published
2019
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46. Genotypic tropism testing by massively parallel sequencing: qualitative and quantitative analysis

Author

Thiele Bernhard, Lengauer Thomas, Klein Rolf, Kaiser Rolf, Däumer Martin, and Thielen Alexander

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Inferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4) variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing. Massively parallel sequencing (MPS) detects single clones thereby being much more sensitive. Using this technology we wanted to improve genotypic prediction of coreceptor usage. Methods Plasma samples from 55 antiretroviral-treated patients tested for coreceptor usage with the Monogram Trofile Assay were sequenced with standard population-based approaches. Fourteen of these samples were selected for further analysis with MPS. Tropism was predicted from each sequence with geno2pheno[coreceptor]. Results Prediction based on bulk-sequencing yielded 59.1% sensitivity and 90.9% specificity compared to the trofile assay. With MPS, 7600 reads were generated on average per isolate. Minorities of sequences with high confidence in CXCR4-usage were found in all samples, irrespective of phenotype. When using the default false-positive-rate of geno2pheno[coreceptor] (10%), and defining a minority cutoff of 5%, the results were concordant in all but one isolate. Conclusions The combination of MPS and coreceptor usage prediction results in a fast and accurate alternative to phenotypic assays. The detection of X4-viruses in all isolates suggests that coreceptor usage as well as fitness of minorities is important for therapy outcome. The high sensitivity of this technology in combination with a quantitative description of the viral population may allow implementing meaningful cutoffs for predicting response to CCR5-antagonists in the presence of X4-minorities.

Published
2011
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47. The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Author

Berg Thomas, Däumer Martin, Tappe André, Stürmer Martin, Kaiser Rolf, Walter Hauke, Ehret Robert, Vachta Jan, Wiesmann Frank, Naeth Gudrun, Braun Patrick, and Knechten Heribert

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.

Published
2011
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48. Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance

Author

Fun, Axel, Leitner, Thomas, Vandekerckhove, Linos, Däumer, Martin, Thielen, Alexander, Buchholz, Bernd, Hoepelman, Andy I.M., Gisolf, Elizabeth H., Schipper, Pauline J., Wensing, Annemarie M.J., Nijhuis, Monique, Fun, Axel, Leitner, Thomas, Vandekerckhove, Linos, Däumer, Martin, Thielen, Alexander, Buchholz, Bernd, Hoepelman, Andy I.M., Gisolf, Elizabeth H., Schipper, Pauline J., Wensing, Annemarie M.J., and Nijhuis, Monique

Published
2018

49. Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTi m e HIV-1 Reference Assay

Author

Wiesmann, Frank, primary, Ehret, Robert, additional, Naeth, Gudrun, additional, Däumer, Martin, additional, Fuhrmann, Jörg, additional, Kaiser, Rolf, additional, Noah, Christian, additional, Obermeier, Martin, additional, Schalasta, Gunnar, additional, Tiemann, Carsten, additional, Wolf, Eva, additional, Knechten, Heribert, additional, and Braun, Patrick, additional

Published
2018
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50. Rapid Rebound of a Preexisting CXCR4-tropic Human Immunodeficiency Virus Variant After Allogeneic Transplantation With CCR5 Δ32 Homozygous Stem Cells

Author

Verheyen, Jens, primary, Thielen, Alexander, additional, Lübke, Nadine, additional, Dirks, Miriam, additional, Widera, Marek, additional, Dittmer, Ulf, additional, Kordelas, Lambros, additional, Däumer, Martin, additional, de Jong, Dorien C M, additional, Wensing, Annemarie M J, additional, Kaiser, Rolf, additional, Nijhuis, Monique, additional, and Esser, Stefan, additional

Published
2018
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