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Günthard

Fakultäten » Medizinische Fakultät » Infektionskrankheiten und Spitalhygiene, Klinik für » Prof. Dr. Huldrych Günthard » Günthard

Completed research project

Title / Titel HIV-1 drug resistance in the Swiss HIV Cohort Study: Epidemiology and impact on the management of HIV infected patients
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung In this project we will perform a comprehensive longitudinal analysis on genotypic HIV-1 drug resistance in Switzerland. Over the last 10 years it has been increasingly appreciated that HIV-1 drug resistance is one of the key factors limiting treatment success and potentially, contributing to the spread of the infection. This scientific project builds on the infrastructure of the Swiss HIV Cohort Study (SHCS) which over the last years has built a large genotypic drug resistance database including almost all genotypic drug resistance information that has been generated in Switzerland over the last years. The resistance data was linked to the wealth of demographic and clinical data included in the SHCS database.
The first objective of our proposal is to obtain a clear picture of incidence, prevalence and changing patterns of HIV-1 drug resistance over the years and to define the impact of transmission of drug resistant strains on the Swiss HIV-1 epidemic. It is important to identify early trends in emergence of drug resistance in the present situation with continuously changing treatment regimens and introduction of new drugs. Furthermore, unravelling the frequency and time trends of transmission of HIV-1 drug resistant strains will be of importance to develop future treatment and prevention strategies.
In the second objective the impact of HIV-1 drug resistance on treatment will be studied. In particular, we will focus on defining mutations which are associated with treatment failure after newly approved drugs are available. Further emphasis will be on determining mutational patterns associated with reduced viral replication in vivo.
In the third objective, we will define predictors of HIV-1 drug resistance with the ultimate goal to prevent the emergence of drug resistance as much as possible in the future. In addition, we will study potential differences in the emergence of drug resistance among different HIV-1 subtypes.
In conclusion, this proposal will harness the cumulative expertise of experts in HIV care, in clinical research, in virology, in bio-statistics and in bioinformatics to the wealth of resistance and clinical information from the SHCS to rigorously study fundamental questions in the fields of HIV drug resistance and treatment. These studies will substantially improve our understanding of the emergence and impact of HIV-1 drug resistance in the Swiss HIV-1 epidemic and will allow us to adapt and improve future prevention and treatment strategies which ultimately will result in a better control of the epidemic and better treatment outcomes.
Publications / Publikationen Haupts S, Ledergerber B, Böni J, Schüpbach J, Kronenberg A, Opravil M, Flepp M, Speck RF, Grube C, Rentsch K, Weber R, and Günthard HF, and the Swiss HIV Cohort Study. Impact of genotypic resistance testing on selection of salvage regimen in clinical practice. Antiviral Therapy. 2003;8:443-454.

Yerly S, Fagard C, Günthard HF, Hirschel B, Perrin L, and the Swiss HIV Cohort Study (SHCS). Selection of HIV-1 drug-resistance mutations during structured treatment interruptions. Antiviral Therapy. 2003;8:411-415.

Metzner KJ, Bonhoeffer S, Fischer M, Karanicolas R, Weber R, Hirschel B, Kostrikis LG, Günthard HF, and the Swiss HIV Cohort Study. Emergence of minor populations of HIV-1 carrying the M184V and L90M mutations in subjects undergoing structured treatment interruptions. Journal of Infectious Diseases. 2003;188:1433-1443.

Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ. Evidence for positive epistasis in HIV-1.Science. 2004;306:1547-50.

Vora S, Marcelin AG, Günthard HF, Flandre P, Hirsch HH, Vernazza P, Furrer H, Masquelier B, Zinkernagel A, Peytavin G, Calvez V, Hirschel B, Perrin L, Yerly S, and the Swiss HIV Cohort Study (SHCS). Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients. AIDS. 2006;20:35-40

Simcock M, Sendi P, Ledergerber B, Keller T, Schüpbach J, Battegay M, Günthard HF, and the Swiss HIV Cohort Study. A longitudinal analysis of health care costs after treatment optimisation following genotypic antiretroviral resistance testing: does resistance testing pay off? Antiviral Therapy. 2006;(in press)

Keywords / Suchbegriffe HIV-1, genotypic drug resistance, viral evolution, antiretroviral treatment, treatment response, treatment failure, viral subtypes
Project leadership and contacts /
Projektleitung und Kontakte
PD Huldrych Günthard, MD (Project Leader) huldrych.guenthard@usz.ch
Research Associate Sabine Yerly, MS sabine.yerly@hcuge.ch
PD Bruno Ledergerber, PhD bruno.ledergerber@usz.ch
Professor Sebastian Bonhoeffer, PhD seb@env.ethz.ch
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung)
SNF Project No 3247B0-112594/1
In collaboration with /
In Zusammenarbeit mit
Swiss HIV Cohort Study Switzerland
PD Dr. Jürg Böni, Prof. Jörg, Schüpbach, Swiss National Reference Center for Retroviruses, University of Zürich,

Dr. Philip Burgisser, CHUV, Lausanne

PD Dr. Thomas Klimkait, Institute of Microbiology, University of Basel,

Prof. Luc Perrin, Laboratory of Virology, HCUGE, Geneva
Switzerland
Duration of Project / Projektdauer May 2006 to Apr 2009