33CS30_148522; Swiss HIV Cohort Study (SHCS); large nested project; viral variants; viral sequence traits; viral set-point; primary HIV infection; large nested project; 33CS30_148522; envelope; HIV-1; transmission; phylogeny; transmitter founder; Swiss HIV Cohort Study (SHCS)
Kadelka Claus, Liechti Thomas, Ebner Hanna, Schanz Merle, Rusert Peter, Friedrich Nikolas, Stiegeler Emanuel, Braun Dominique L., Huber Michael, Scherrer Alexandra U., Weber Jacqueline, Uhr Therese, Kuster Herbert, Misselwitz Benjamin, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, et al. (2018), Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity, in The Journal of Experimental Medicine
, 215(6), 1589-1608.
Kühnert Denise, Kouyos Roger, Shirreff George, Pečerska Jūlija, Scherrer Alexandra U, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Günthard Huldrych F, Stadler Tanja, Bonhoeffer Sebastian, Bonhoeffer Sebastian (2018), Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics., in PLoS pathogens
, 14(2), 1006895-1006895.
Braun Dominique L, Marzel Alex, Steffens Daniela, Schreiber Peter W, Grube Christina, Scherrer Alexandra U, Kouyos Roger D, Günthard Huldrych F, Günthard Huldrych F (2018), High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky Sexual Behavior in Patients Initially Presenting With Primary Human Immunodeficiency Virus-1 Infection., in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
, 66(5), 735-742.
Bertels Frederic, Marzel Alex, Leventhal Gabriel, Mitov Venelin, Fellay Jacques, Günthard Huldrych F, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Battegay Manuel, Rauch Andri, Cavassini Matthias, Calmy Alexandra, Bernasconi Enos, Schmid Patrick, Scherrer Alexandra U, Müller Viktor, Bonhoeffer Sebastian, Kouyos Roger, Regoes Roland R, Regoes Roland R (2018), Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity., in Molecular biology and evolution
, 35(1), 27-37.
Turk Teja, Bachmann Nadine, Kadelka Claus, Böni Jürg, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Battegay Manuel, Bernasconi Enos, Calmy Alexandra, Cavassini Matthias, Furrer Hansjakob, Hoffmann Matthias, Günthard Huldrych F, Kouyos Roger D, Kouyos Roger D, Aubert V, Battegay M, Bernasconi E, Böni J, 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, Haerry D, Hasse B, Hirsch H H, Hoffmann M, Hösli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kouyos R D, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Marzolini C, Metzner K J, Müller N, Nicca D, Pantaleo G, Paioni P, Rauch A, Rudin C, Scherrer A U, Schmid P, Speck R, Stöckle M, Tarr P, Trkola A, Vernazza P, Wandeler G, Weber R, Yerly S (2017), Assessing the danger of self-sustained HIV epidemics in heterosexuals by population based phylogenetic cluster analysis., in eLife
, 6, 1-47.
Brandenberg Oliver F., Magnus Carsten, Rusert Peter, Guenthard Huldrych F., Regoes Roland R., Trkola Alexandra (2017), Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters, in PLOS PATHOGENS
, (5), 1.
Bachmann Nadine, Turk Teja, Kadelka Claus, Marzel Alex, Shilaih Mohaned, Boni Jurg, Aubert Vincent, Klimkait Thomas, Leventhal Gabriel E., Gunthard Huldrych F., Kouyos Roger (2017), Parent-offspring regression to estimate the heritability of an HIV-1 trait in a realistic setup, in RETROVIROLOGY
Hoenigl Martin, Braun Dominique L., Kouyos Roger, Guenthard Huldrych F., Little Susan J. (2017), Evaluation of the Predictive Potential of the Short Acute Retroviral Syndrome Severity Score for HIV-1 Disease Progression in Individuals With Acute HIV Infection, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
, (4), 114-117.
Marzel Alex, Heinrich Henriette, Schilliger Lukas, Fehr Jan S., Guenthard Huldrych F., Kouyos Roger, Rampini Silvana K. (2017), Prescription of Postexposure Prophylaxis for HIV-1 in the Emergency Room: Correct Transmission Risk Assessment Remains Challenging, in JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
, (4), 359-366.
Rasmussen David A., Kouyos Roger, Gunthard Huldrych F., Stadler Tanja (2017), Phylodynamics on local sexual contact networks, in PLOS COMPUTATIONAL BIOLOGY
, (3), 1.
Shilaih Mohaned, Marzel Alex, Braun Dominique L., Scherrer Alexandra U., Kovari Helen, Young Jim, Calmy Alexandra, Darling Katharine, Battegay Manuel, Hoffmann Matthias, Bernasconi Enos, Thurnheer Maria C., Gunthard Huldrych F., Kouyos Roger D. (2017), Factors associated with syphilis incidence in the HIV-infected in the era of highly active antiretrovirals, in MEDICINE
, (2), 1.
Günthard Huldrych F, Scherrer Alexandra U (2016), HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug Resistance., in The Journal of infectious diseases
, (9), 1289-1291.
Ragonnet-Cronin Manon L., Shilaih Mohaned, Gunthard Huldrych F., Hodcroft Emma B., Boni Jurg, Fearnhill Esther, Dunn David, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Yang Wan-Lin, Brown Alison E., Lycett Samantha J., Kouyos Roger, Brown Andrew J. Leigh (2016), A Direct Comparison of Two Densely Sampled HIV Epidemics: The UK and Switzerland, in SCIENTIFIC REPORTS
Oberle Corinna S., Joos Beda, Rusert Peter, Campbell Nottania K., Beauparlant David, Kuster Herbert, Weber Jacqueline, Schenkel Corinne D., Scherrer Alexandra U., Magnus Carsten, Kouyos Roger, Rieder Philip, Niederost Barbara, Braun Dominique L., Pavlovic Jovan, Boni Jurg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Trkola Alexandra, Metzner Karin J., Gunthard Huldrych F. (2016), Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs, in RETROVIROLOGY
Scherrer Alexandra U., Yang Wan-Lin, Kouyos Roger D., Boni Jurg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Cavassini Matthias, Battegay Manuel, Hauser Christoph, Calmy Alexandra, Schmid Patrick, Bernasconi Enos, Gunthard Huldrych F. (2016), Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study, in JOURNAL OF INFECTIOUS DISEASES
, (3), 399-402.
Scherrer Alexandra U., von Wyl Viktor, Yang Wan-Lin, Kouyos Roger D., Boni Jurg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Cavassini Matthias, Battegay Manuel, Furrer Hansjakob, Calmy Alexandra, Vernazza Pietro, Bernasconi Enos, Gunthard Huldrych F. (2016), Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis, in CLINICAL INFECTIOUS DISEASES
, (10), 1310-1317.
Noguera-Julian M., Cozzi-Lepri A., Di Giallonardo F., Schuurman R., Daumer M., Aitken S., Ceccherini-Silberstein F., Monforte A. D'Arminio, Geretti A. M., Booth C. L., Kaiser R., Michalik C., Jansen K., Masquelier B., Bellecave P., Kouyos R. D., Castro E., Furrer H., Schultze A., Guenthard H. F., Brun-Vezinet F., Metzner K. J., Paredes R. (2016), Contribution of APOBEC3G/F activity to the development of low-abundance drug-resistant human immunodeficiency virus type I variants, in CLINICAL MICROBIOLOGY AND INFECTION
, (2), 191-200.
Villandre Luc, Stephens David A., Labbe Aurelie, Guenthard Huldrych F., Kouyos Roger, Stadler Tanja (2016), Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1, in PLOS ONE
, (2), 1.
Montazeri H Kuipers J Kouyos RD Böni J Yerly S Klimkait T Aubert V Günthard HF (2016), Large-scale inference of conjunctive Bayesian networks, in Bioinformatics
Marzel Alex, Shilaih Mohaned, Yang Wan-Lin, Boeni Juerg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Braun Dominique L., Calmy Alexandra, Furrer Hansjakob, Cavassini Matthias, Battegay Manuel, Vernazza Pietro L., Bernasconi Enos, Guenthard Huldrych F., Kouyos Roger D. (2015), HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study, in CLINICAL INFECTIOUS DISEASES
, (1), 115-122.
Yang Wan-Lin, Kouyos Roger D, Scherrer Alexandra U, Böni Jürg, Shah Cyril, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Hirzel Cédric, Battegay Manuel, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro, Held Leonhard, Ledergerber Bruno, Günthard Huldrych F, Günthard Huldrych F, Günthard Huldrych F (2015), Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study., in The Journal of antimicrobial chemotherapy
, 70(12), 3323-31.
Montazeri Hesam, Guenthard Huldrych F., Yang Wan-Lin, Kouyos Roger, Beerenwinkel Niko (2015), Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance, in BIOSTATISTICS
, (4), 713-726.
Braun Dominique L., Kouyos Roger D., Balmer Belinda, Grube Christina, Weber Rainer, Guenthard Huldrych F. (2015), Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection, in CLINICAL INFECTIOUS DISEASES
, (6), 1013-1021.
Kohler Ines, Kouyos Roger, Bianchi Matteo, Grube Christina, Wyrzucki Arkadiusz, Guenthard Huldrych F., Hangartner Lars (2015), The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals, in AIDS
, (14), 1803-1810.
Kouyos Roger D., Guenthard Huldrych F. (2015), The Irreversibility of HIV Drug Resistance, in CLINICAL INFECTIOUS DISEASES
, (5), 837-839.
Kouyos R Hasse B Calmy A Cavassini M Furrer H Stöckle M Vernazza PL Bernasconi E Weber R Gü (2015), Increases in condomless sex i the Swiss HIV Cohort Study, in Open Forum Infectious Diseases
This translational research project is a continuation of SNF 130865. We aim to unravel traits of HIV transmission in three conceptually different situations of high clinical relevance: transmission leading to de novo infection (Aim 1), spread of HIV between infected individuals (conferred to as superinfection (SI); Aim 2) and transmission of drug resistant virus (Aim 3). The proposed studies are based on two renowned longitudinal studies with extensive biobanks: The Swiss HIV Cohort and the Zurich Primary HIV-1 infection study (ZPHI). AIM 1. Here we will determine whether specific genotypic and phenotypic viral traits of transmitted/founder viruses (T/F) exist. Characterization of T/F viruses, the earliest virus population that emerges in a newly infected individual, is of high interest as understanding their transmis-sion pathways may open avenues for prophylaxis and treatment. Current data on T/F virus features led to intriguing in-sights, but no definitive picture of genetic and phenotypic traits of T/F viruses has emerged. A limitation of previous studies was that features of T/F viruses had to be compared to unrelated viruses from chronically infected patients as transmitting individuals were in most cases not identified. Here using phylogenetically linked T/F viruses and their transmitters we will be able to study phylogenetically linked transmitter-recipient pairs. Thus far we identified 79 acutely HIV infected (recipients) and 107 chronically infected individuals with genetically related HIV strains which are their likely transmitters. Plasma samples close to estimated time of infection will be chosen for virus genomic analysis from transmitters and recipients to retrieve full length HIV-genomes employing Next Generation Sequencing (NGS) followed by haplotype reconstruction. T/F virus will be compared to variants present in the transmitter regarding, length, specific mutations, deletions/insertions, glycosylation sites, charge and frequency to define whether stochastic or non-stochastic transmission occurs. If genotypic traits are identified, gene transfer and mutagenesis experiments will be performed followed by phenotypic analysis to discern if indeed signifying characteristics of T/F viruses exist. To this end we will compare transmitter and T/F viruses for features implicated in shaping transmission including replication capacity, sensitivity to neutralizing antibodies and entry inhibitors, entry kinetics and interferon sensitivity. AIM 2: Here we will systematically explore frequency and risk factors for HIV-1 superinfection in the SHCS and ZPHI. A first phylogenetic screen based on pol sequences has revealed 150-312 potential SI cases. By retrieving longitudinal plasma samples before patients went on antiretroviral therapy we will seek to confirm SI by full length NGS and define approximate time points of SI events. In a detailed virus genomic analysis we aim to reconstruct haplotypes, study recombination events. A specific emphasis of our studies is on determining risk factors for acquiring SI using detailed patient, disease and host genomic data available. Viral fitness of initial circulating and superinfecting strains will be computed using machine learning techniques. To test whether SI is prevented by neutralizing antibody responses, those will be compared among superinfected and non-superinfected individuals. Finally, viral setpoint of cases and controls will be compared to determine the impact of SI on disease progression. AIM 3: Here we will investigate transmission of HIV-1 drug resistance mutations (TDR) within the SHCS, specifically focussing on the non-B compared to the subtype B epidemic, newer drugs, and reversion rates of TDR. We will study TDR prevalence over time for B and non- B subtypes in all drug naives and, specifically, in recently infected individuals. We will particularly focus on newer drugs. In patients with TDR we will determine reversion rates for specific TDR and fitness cost by taking into account the pol genotypic backbone indepen-dently of TDR. Furthermore, by performing phylogenetic analysis we will study whether there are differences in transmission dynamics between B- and non-B subtype TDR. This analysis will reveal whether TDR in the non-B subtypes is increasing as would be expected due to the recent, wide spread roll out of antiretroviral drugs in developing countries.