Zurich Primary HIV Infection Cohort Study (ZPHI)

 

Despite a considerable body of knowledge that has been accumulated over the past decades and major successes in the treatment of HIV infection, neither an effective vaccine nor an eradication of HIV by drug intervention are within reach. Current antiretroviral treatment (ART) has dramatically reduced morbidity and development of AIDS in industrialized countries. To date however success of ART necessitates a life-long, continuous therapy as drug control the virus but cannot eliminate it form the latent reservoir. In order to control HIV-1 infection in the future, three main pillars are necessary: i) Optimal treatment of patients to control disease and limit transmission, ii) Resolving the underlying biology that leads to HIV latency to allow development of novel therapies leading to eradication of HIV from the infected individual (cure). iii) Defining protective immune responses against HIV to allow the development of effective vaccines. A key focus of research to reach these goals is the acute HIV infection as during this stage the latent reservoir is formed and the immune system is primed.

The research of acute HIV Infection is the key focus of the Zurich Primary HIV Infection Study (ZPHI). The ZPHI is an open label, non-randomized, observational, monocenter study at the University Hospital Zurich, Division of Infectious Diseases and Hospital Epidemiology and has been started at the beginning of 2002. The ZPHI is conducted by Prof. Huldrych Günthard. Since 2002, the ZPHI has enrolled more than 360 patients with a documented primary HIV infection (PHI). Recruitment of patients with a PHI into the ZPHI is ongoing. The ZPHI aims to describe the epidemiology of PHI, to longitudinally follow patients with a PHI, to test the effect of early antiretroviral treatment (ART) and to investigate clinical presentation and early events of virus-host interactions in patients with a documented PHI in Zurich.

The ZPHI belongs to the largest PHI studies in the western world, including well-described patients defined by using very strict PHI criteria. The ZPHI has published more than 50 original articles and reviews within the last ten years. The research platform of the ZPHI-study includes internationally renowned research groups within the areas of clinical infectious diseases, basic virology, immunology, genetics, evolution and bioinformatics research. Through this platform we have the possibility to perform innovative, pathogenesis-oriented clinical trials and basic research centering around HIV transmission, formation of the viral reservoir and its eradication. The platform further provides interesting training opportunities for master students (Medicine and Faculty of Science), PhD, MD-PhD students, postdocs and clinical researchers in different disciplines (microbiology, immunology, epidemiology / Biostatistics, Bioinformatics / Biomathematics, infectious diseases).

Areas of interest within the Zurich Primary HIV Infection Study
Clinical/epidemiological research:
• Optimal treatment of acute HIV-1 infection.
• Performance of clinical trials for studying various eradication-strategies in regard to reducing the latent reservoir.
• Study of the early clinical presentation during acute HIV infection.
• Study of the transmission of other sexually transmitted diseases (e.g., syphilis, chlamydia, gonorrhea, hepatitis C virus infection).
• Identification of transmission networks within and outside the ZPHI by molecular-epidemiological methods to start targeted prevention.
• Study of the transmission and development of drug resistance.
• Clarify the question regarding transmission of drug resistant minority variants during the acute HIV infection or de novo evolution of drug resistant minority variants.

Translational:
• Identification of biological characteristics of the transmitted viruses.
• Identification of "Transmission Pairs" and studies of HIV in the "transmitter" and "Recipient".
• Characterization of residual transcription/virus production under antiretroviral therapy.
• Study of Virus - host interactions.
• Identification of human genetic patterns that may be associated with acute retroviral syndrome.
• Molecular characterization of newly transmitted viruses in ZPHI patients infected with hepatitis C virus using NGS technology.

Basic science:
• B-cell function and maturation of the humoral immune response during the acute and in the chronic phase of HIV infection.
• Co-stimulation and immune activation of non HIV-1-infected CD4 and CD8 cells during the HIV-specific cellular immune response.
• Studies of mechanisms of immune-activation under anti-retroviral therapy.
• Inter-versus intra-host evolution of HIV.
• Studies of viral latency.
• Identification of small non-coding RNAs HIV and possible role in the regulation of the same on HIV-1 or HIV replication latency.

ZPHI Study - the heart of many research projects

 


Publications

Information and Secretary

Tel.+41 44 255 33 22
Fax +41 44 255 44 99

Team

• Prof Dr. med. Huldrych Günthard, senior staff physician division of infectious diseases and hospital epidemiology, head of the HIV research laboratory, president of the shcs
• Prof. Karin Metzner, head of laboratory group
• Prof. Roger Kouyos, head of laboratory group
• Dr. med. Dominique Braun, research attending physician
• Christina Grube, study nurse
• Dr. med. Michael Greiner, fellow for infectious diseases and hospital epidemiology
• Dr. med. Daniela Bircher, fellow for  infectious diseases and hospital epidemiology
• Herbert Kuster, head of laboratory
• Dominique Klimpel, laboratory assistant
• Christine Leemann, laboratory assistant
• Stefan Schmutz, laboratory assistant
• Chantal von Siebenthal, laboratory assistant
• Corinne Schenkel, laboratory assistant
• Dr. Valentina Vongrad, Postdoc
• Dr. Alexandra Scherrer, Postdoc
• Nottania Campbell, PhD student
• Corinna Oberle, PhD student
• Victoria Strouvelle, PhD student
• Yik Lim Kok, PhD student
• Alex Marzel, PhD student
• Mohaned Shilaih, PhD student

Collaboration Research

• http://www.viralinfectiousdiseases.uzh.ch/ZPHI.html
• Group Günthard
• http://www.en.infektiologie.usz.ch/LehreUndForschung/Group_Metzner/Pages/default.aspx
• http://www.en.infektiologie.usz.ch/LehreUndForschung/GroupMueller/Pages/default.aspx
• http://www.virology.uzh.ch/index.html
• https://www1.ethz.ch/bsse/cbg
• http://www.tb.ethz.ch/research/bonhoeffer-group.html
• http://www.micro.biol.ethz.ch/research/oxenius
• http://fellay-lab.epfl.ch/
• www.shcs.ch

Contact

Division of Infectious Diseases and Hospital Epidemiology
University Hospital Zurich
Prof. Dr. med. H. Günthard
Rämistrasse 100
8091 Zürich