ZPHI Study

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. With worldwide numbers of people living with HIV constantly increasing, associated costs of therapies put a tremendous pressure on health care systems. Additionally, side effects of long term therapy only solely become understood and more and more co-morbidities need to be considered as we go along. 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. This is the main focus of the Zurich Primary HIV Study (ZPHI), which is imbedded in the KFSP Viral Infectious Diseases. The research platform of the KFSP-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).

KFSP Zurich Primary HIV Infection Study

Project leader subproject ZPHI Study

Prof. H. Günthard

Research groups

Prof. H. Günthard
PD Dr. K. Metzner
Prof. A. Trkola
Prof. N. Müller
Prof. A. Telenti
Prof. J. Fellay
Prof. N. Beerenwinkel
Prof. S. Bonhoeffer
Prof. A. Oxenius

Clinical/epidemiological research:

• Optimal treatment of acute HIV-1 infection
• Study of the early clinical presentation during acute HIV infection (development of an "acute retroviral syndrome (ARS) severity scores" (ARSS))
• Study of the transmission of other sexually transmitted diseases (syphilis, chlamydia, GO and currently highly controversial: Hepatitis C among MSM)
• Identification of transmission networks within and outside the ZPHI by molecular-epidemiological methods to start targeted prevention.
• Transmission and development of drug resistance (impact of "minority drug resistant variants" on treatment response)
• Clarify the question regarding transmission of drug resistant minority variants during the acute HIV infection or de novo evolution of drug resistant minority variants.
• Development of clinical trial protocols for studying various eradication-strategies in regard to reducing the latent reservoir

Translational:

• Identification of biological characteristics of the transmitted viruses (phenotypic and genotypic characterization of virus isolates)
• Identification of "Transmission Pairs" and studies of HIV in the "transmitter" and "Recipient" (phenotypically and genotypically)
• Characterization of residual transcription/virus production under antiretroviral therapy
• Virus - host interactions (full length sequencing of HIV-1 by next generation sequencing (NGS) and Genome Wide Association Studies (GWAS) of ZPHI patients)
• Identification of human genetic patterns that may be associated with ARSS (host genotyping for rare variants with new high-resolution exome chip)
• Molecular characterization of newly transmitted viruses in ZPHI HCV patients using NGS technology

Basic science:

• B-cell function and maturation of the humoral immune response during the acute and in the chronic phase
• 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 such us bacterial translocation and co-stimulation with other herpes-viruses latently infected T lymphocytes
• Inter-versus intra-host evolution of HIV (NGS for partial and full-length HIV genome with Haplotype-reconstruction for HIV quasispecies)
• Studies of viral latency (transcription status of various immune cells, integration pattern of HIV proviruses in different cell types
• Identification of small non-coding RNAs HIV and possible role in the regulation of the same on HIV-1 or HIV replication latency)