Project

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Combining molecular epidemiology approaches and mathematical models for the spread of HIV and its coinfections

Applicant Kouyos Roger
Number 142411
Funding scheme Ambizione
Research institution Klinik für Infektionskrankheiten und Spitalhygiene Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Infectious Diseases
Start/End 01.10.2012 - 30.09.2015
Approved amount 552'848.00
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Keywords (4)

Drug resistance; HIV; Transmission; Molecular Epidemiology

Lay Summary (English)

Lead
Lay summary

Molecular epidemiology characterizes the spread of infectious agents on the basis of their nucleotide sequences. This can be done because the similarity of sequences sampled from different patients correlates with the proximity of those patients in the transmission chain of the pathogen. In other words, the closer two patients are in the transmission chain of a pathogen the more similar are the sequences of the pathogens sampled from these two patients. The power of molecular epidemiology approaches is however often limited because the nucleotide sequences are not linked to the broader epidemiological and clinical context of the pathogen.

The aim of the proposed research is to combine molecular epidemiology approaches with clinical data and mathematical models in order to investigate the transmission of HIV and its co-infections in Switzerland. This research will use the unique data from the Swiss HIV Cohort Study to investigate the following four questions:

1) Is there a hidden HIV epidemic in Switzerland? In particular, we will use HIV sequences to investigate whether there are transmission networks of HIV that are systematically missed by the current disease surveillance.

2) How does the spread of HIV and Hepatitis C Virus (HCV) interact? A substantial proportion of people infected with HIV are also infected with HCV. We will use mathematical models to describe the current trends of HCV co-infections among the HIV-infected individuals in Switzerland. In addition, we will use phylogenetic trees to identify the transmission routes driving the spread of HCV.

3) How important is the early phase of the HIV infection for the epidemic spread of the virus? Transmission in the early phase of the HIV infection is an important challenge for public health because most patients do not know about their infections in that phase. In order to assess the importance of acute HIV infection in Switzerland we will combine epidemiological data with HIV sequence data and fit these combined data with mathematical models that can capture the role of early infection.  

4) How likely is a spread of drug-resistant HIV strains in resource-limited settings and how high is the potential impact of such a spread on Switzerland? This work will use mathematical models that combine the spread and evolution of HIV to assess this potential scenario.  


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
A Direct Comparison of Two Densely Sampled HIV Epidemics: The UK and Switzerland
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, 6, doi:10.103.
Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1
Villandre Luc, Stephens David A., Labbe Aurelie, Guenthard Huldrych F., Kouyos Roger, Stadler Tanja, Study Swiss HIV Cohort (2016), Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1, in PLOS ONE, 11(2), NA.
Can we believe the DAGs? A comment on the relationship between causal DAGs and mechanisms
Aalen O. O., Roysland K., Gran J. M., Kouyos R., Lange T. (2016), Can we believe the DAGs? A comment on the relationship between causal DAGs and mechanisms, in STATISTICAL METHODS IN MEDICAL RESEARCH, 25(5), 2294-2314.
Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis
Shilaih Mohaned, Marzel Alex, Scherrer Alexandra U., Braun Dominique L., Kovari Helen, Rougemont Mathieu, Darling Katharine, Battegay Manuel, Hoffmann Matthias, Bernasconi Enos, Hirzel Cedric, Gunthard Huldrych F., Kouyos Roger D., Study Swiss HIV Cohort (2016), Dually Active HIV/HBV Antiretrovirals as Protection Against Incident Hepatitis B Infections: Potential for Prophylaxis, in JOURNAL OF INFECTIOUS DISEASES, 214(4), 599-606.
Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis
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., Study Swiss HIV Cohort (2016), Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis, in CLINICAL INFECTIOUS DISEASES, 62(10), 1310-1317.
Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland
Shilaih Mohaned, Marzel Alex, Yang Wan Lin, Scherrer Alexandra U., Schupbach Jorg, Boni Jurg, Yerly Sabine, Hirsch Hans H., Aubert Vincent, Cavassini Matthias, Klimkait Thomas, Vernazza Pietro L., Bernasconi Enos, Furrer Hansjakob, Gunthard Huldrych F., Kouyos Roger, Study Swiss HIV Cohort (2016), Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland, in SCIENTIFIC REPORTS, 6, doi:10.103.
Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period
Aebi-Popp K., Kouyos R., Bertisch B., Staehelin C., Rudin C., Hoesli I., Stoeckle M., Bernasconi E., Cavassini M., Grawe C., Lecompte T. D., Rickenbach M., Thorne C., de Tejada B. Martinez, Fehr J., & Child HIV Cohort St Swiss Mother (2016), Postnatal retention in HIV care: insight from the Swiss HIV Cohort Study over a 15-year observational period, in HIV MEDICINE, 17(4), 280-288.
Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study
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., Study Swiss HIV Cohort (2016), Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study, in JOURNAL OF INFECTIOUS DISEASES, 214(3), 399-402.
The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB
Cadosch Dominique, zur Wiesch Pia Abel, Kouyos Roger, Bonhoeffer Sebastian (2016), The Role of Adherence and Retreatment in De Novo Emergence of MDR-TB, in PLOS COMPUTATIONAL BIOLOGY, 12(3), http://dx..
Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study
Yang Wan-Lin, Kouyos Roger D., Scherrer Alexandra U., Boeni Juerg, Shah Cyril, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Hirzel Cedric, Battegay Manuel, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro, Held Leonhard, Ledergerber Bruno, Guenthard Huldrych F., Study Swiss HIV Cohort (2015), Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study, in JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 70(12), 3323-3331.
Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012
Yang Wan-Lin, Kouyos Roger, Scherrer Alexandra U., Boeni Juerg, Shah Cyril, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Furrer Hansjakob, Battegay Manuel, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro, Held Leonhard, Ledergerber Bruno, Guenthard Huldrych F., Study Swiss HIV Cohort (2015), Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012, in JOURNAL OF INFECTIOUS DISEASES, 212(1), 28-38.
Frequency and Spectrum of Unexpected Clinical Manifestations of Primary HIV-1 Infection
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, 61(6), 1013-1021.
HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.
Marzel Alex, Shilaih Mohaned, Yang Wan-Lin, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Braun Dominique L, Calmy Alexandra, Furrer Hansjakob, Cavassini Matthias, Battegay Manuel, Vernazza Pietro L, Bernasconi Enos, Günthard Huldrych F, Kouyos Roger D, {Swiss HIV Cohort Study} (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 : an official publication of the Infectious Diseases Society of America, 10.1093/ci.
Increases in Condomless Sex in the Swiss HIV Cohort Study
Kouyos R D, Hasse B., Calmy A, Cavassini M., Furrer H, Stockle M, Vernazza P L, Bernasconi E., Weber R, Günthard H F, {and the Swiss HIV Cohort Study} (2015), Increases in Condomless Sex in the Swiss HIV Cohort Study, in Open Forum Infectious Diseases, 2(2), 077-077.
Modeling the effect of HIV coinfection on clearance and sustained virologic response during treatment for hepatitis C virus
Birger Ruthie, Kouyos Roger, Dushoff Jonathan, Grenfell Bryan (2015), Modeling the effect of HIV coinfection on clearance and sustained virologic response during treatment for hepatitis C virus, in Epidemics, 1.
Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds.
Yang Wan-Lin, Kouyos Roger D, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Scherrer Alexandra U., Shilaih Mohaned, Hinkley Trevor, Petropoulos Christos, Bonhoeffer Sebastian, Günthard Huldrych F, {Swiss HIV Cohort Study (SHCS)} (2015), Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds., in PLoS pathogens, 11(3), 1004722-1004722.
The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals
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, 29(14), 1803-1810.
The Irreversibility of HIV Drug Resistance.
Kouyos Roger D, Günthard Huldrych F (2015), The Irreversibility of HIV Drug Resistance., in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 10.1093/ci.
The potential impact of coinfection on antimicrobial chemotherapy and drug resistance
Birger Ruthie B., Kouyos Roger D., Cohen Ted, Griffiths Emily C., Huijben Silvie, Mina Michael, Volkova Victoriya, Grenfell Bryan, Metcalf C. Jessica E. (2015), The potential impact of coinfection on antimicrobial chemotherapy and drug resistance, in TRENDS IN MICROBIOLOGY, 23(9), 537-544.
The potential impact of coinfection on antimicrobial chemotherapy and drug resistance.
Birger Ruthie B, Kouyos Roger D, Cohen Ted, Griffiths Emily C, Huijben Silvie, Mina Michael, Volkova Victoriya, Grenfell Bryan, Metcalf C Jessica E (2015), The potential impact of coinfection on antimicrobial chemotherapy and drug resistance., in Trends in microbiology, 10.1016/j..
A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression
Braun Dominique L., Kouyos Roger, Oberle Corinna, Grube Christina, Joos Beda, Fellay Jacques, McLaren Paul J., Kuster Herbert, Guenthard Huldrych F. (2014), A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression, in PLOS ONE, 9(12), NA.
Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV.
Kouyos Roger D, Rauch Andri, Böni Jürg, Yerly Sabine, Shah Cyril, Aubert Vincent, Klimkait Thomas, Kovari Helen, Calmy Alexandra, Cavassini Matthias, Battegay Manuel, Vernazza Pietro L, Bernasconi Enos, Ledergerber Bruno, Günthard Huldrych F, Swiss HIV Cohort Study (SHCS) (2014), Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV., in International journal of epidemiology, 43(3), 887-96.
Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.
Kouyos Roger D, Rauch Andri, Braun Dominique L, Yang Wan-Lin, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Shah Cyril, Kovari Helen, Calmy Alexandra, Cavassini Matthias, Battegay Manuel, Vernazza Pietro L, Bernasconi Enos, Ledergerber Bruno, Günthard Huldrych F (2014), Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide., in The Journal of infectious diseases, 210(10), 1555-61.
Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland
Avila Dorita, Keiser Olivia, Egger Matthias, Kouyos Roger, Boeni Juerg, Yerly Sabine, Klimkait Thomas, Vernazza Pietro L., Aubert Vincent, Rauch Andri, Bonhoeffer Sebastian, Guenthard Huldrych F., Stadler Tanja, Spycher Ben D., Study Swiss HIV Cohort (2014), Social Meets Molecular: Combining Phylogenetic and Latent Class Analyses to Understand HIV-1 Transmission in Switzerland, in AMERICAN JOURNAL OF EPIDEMIOLOGY, 179(12), 1514-1525.
Hospital-Community Interactions Foster Coexistence between Methicillin-Resistant Strains of Staphylococcus aureus
Kouyos Roger, Klein Eili, Grenfell Bryan (2013), Hospital-Community Interactions Foster Coexistence between Methicillin-Resistant Strains of Staphylococcus aureus, in PLOS PATHOGENS, 9(2), NA.
Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study.
Drescher Sara M, von Wyl Viktor, Yang Wan-Lin, Böni Jürg, Yerly Sabine, Shah Cyril, Aubert Vincent, Klimkait Thomas, Taffé Patrick, Furrer Hansjakob, Battegay Manuel, Ambrosioni Juan, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro L, Ledergerber Bruno, Günthard Huldrych F, Kouyos Roger D, the Swiss HIV Cohort Study, Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study., in Clinical Infectious Diseases.

Collaboration

Group / person Country
Types of collaboration
Zurich Primary HIV infection study Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Swiss HIV Cohort Study Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Patrick Taffé Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
BSV Database Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Ruthie Birger United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Andri Rauch Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Tanja Stadler Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Olivia Keiser Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Conference On Retroviruses And Opportunistic Infections Individual talk Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide 01.03.2014 Boston, United States of America Kouyos Roger;
Conference On Retroviruses And Opportunistic Infections Poster LOCATION ON HIV PHYLOGENY IS INDICATIVE OF THE RISK OF HCV INFECTION 03.03.2013 Atlanta, United States of America Kouyos Roger;


Self-organised

Title Date Place
Swiss Meeting for Infectious Disease Dynamics 13.09.2013 Zurich, Switzerland

Awards

Title Year
Georg Friedrich Götz-Preis 2016

Associated projects

Number Title Start Funding scheme
148522 Swiss HIV Cohort Study (SHCS) 01.01.2014 Cohort Studies Large
155851 Using transmission networks for assessing and guiding prevention efforts in hiv 01.10.2015 SNSF Starting Grants

Abstract

Molecular epidemiology approaches have made crucial contributions to our understanding of the epidemiology and biology of HIV. However the power of these approaches is often limited because sequence analyses are not linked to the broader epidemiological and clinical context. The aim of the proposed research is to combine molecular epidemiology approaches with clinical data and mathematical models in order to investigate the transmission of HIV and its coinfections. The proposed projects will be carried out in the context of the Swiss HIV Cohort Study (SHCS) Drug Resistance Database. The SHCS is the ideal setting for these projects as it is highly representative for the HIV population in Switzerland and combines sequence and clinical data of extraordinary quality. Concretely, I propose to investigate four aspects of HIV transmission.In the first project, I will assess the completeness of the SHCS and in particular the existence of hidden Swiss sub-epidemics not captured by the common epidemiological surveillance. To this end, I will combine the nucleotide sequences from patients in the SHCS with the sequences from Swiss patients not enrolled in the SHCS and derive transmission clusters from the resulting phylogenetic trees. This approach will allow to detect entire transmission chains missed by the SHCS and to reconstruct the demographic properties of the missed patients. Finally, the interaction between cohort- and non-cohort patients will be quantified by fitting a structured birth-death process to the phylogenetic trees corresponding to the transmission clusters. In the second project, I will investigate the epidemiological interaction between HIV and HCV. I will use a mathematical model for HIV/HCV coinfections in order to assess to what extent HIV coinfections can amplify the epidemic spread of HCV. Essentially, this model will incorporate the well-studied impact of HIV on individual HCV infections and estimate on this basis the population-level effect of coinfections. This is particularly important, as there has been recently a dramatic increase of HCV cases among HIV-infected men that have sex with men (MSM). In addition, I will use the distribution of HCV cases on the HIV phylogeny in order to infer by which transmission route HCV is acquired by the patients enrolled in the SHCS. Finally, I will assess similarities and differences in the epidemic spread of the two infections by directly comparing the composition of the phylogenetically derived transmission clusters for HIV and HCV. In the third project, I will evaluate the contribution of acute HIV infections to HIV transmission. I will start with a micro-scale analysis which will ascertain the relative importance of acute vs. chronic infection by using phylogenetic and clinical data to categorize as many individual infection events as possible as stemming either from an acute or from a chronic infection. In a subsequent macro-scale analysis, I will determine the overall contribution of early infection by fitting population-dynamical models to the phylogenies and infection-time estimates from Swiss transmission clusters. Finally, I will assess to what extent the frequent clustering of acutely infected patients is due to behavioral risk and sampling biases by considering how testing-frequencies and coinfections with other sexually transmitted infections are distributed on these HIV phylogenies. In the last project, I will study the transmission of drug resistant HIV in resource-limited settings and the potential consequences of such a spread for Switzerland. I will assess the probability of a drug resistant HIV epidemic in resource-limited settings by developing an epidemiological model, which integrates parameters values derived from the epidemiological literature. One particular focus of this work will be to evaluate to what extent the differences between antiretroviral therapy (ART) in resource-rich and resource-limited-settings might make the latter more susceptible for the spread of drug resistant HIV. Almost 50% of HIV infections among Swiss heterosexuals are caused by non-B HIV subtypes and are hence strongly linked to resource-limited settings. Accordingly, I will asses in a next step the potential impact that wide-spread drug-resistance in resource-limited countries might have on Switzerland by combining mathematical models of disease spread with phylogenetic analyses characterizing the import and spread of non-B subtypes in Switzerland. Taken together, these projects will improve our understanding of HIV transmission in Switzerland and beyond as well as address important public health questions such as the interaction between HIV and HCV and the spread of antiretroviral resistance.
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