The Federal Ministry of Education and Research (BMBF) initiated the German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung – DZIF) as an integrated multi-centre structure bringing together selected universities, university hospitals, and non-university research institutes to link their strong research portfolios and clinical infrastructure.

The Grand Challenges still provided by infectious diseases in general, and by HIV in particular, are caused by emerging and globally present pathogens, rapid development of resistance against anti-infectives and poverty-associated infectious diseases in developing countries.

These Grand Challenges can only be met by an integrative effort bundling the scientific expertise in basic research, epidemiology, translational research, and clinical studies. In Germany, such expertise in infectious diseases is dispersed throughout the country, translational efforts are scarce and efforts tackling the Grand Challenges are fragmented and not efficient.

The new DZIF will foster the strategic coordination of concerted translational efforts aiming at novel diagnostic, preventive and therapeutic measures against the most important infectious diseases with a special unit dedicated to HIV/AIDS. The translational efforts focusing on distinct infectious disease-related health problems are coordinated by “Thematic Translational Units” (TTUs).

DZIF will cooperate at the national level with agencies responsible for disease prevention (RKI), animal welfare (FLI), licensing of diagnostics and biologicals (PEI) or drugs (BfArM). At the international level DZIF will be a strong partner for international consortia and industry, which will sustainably enforce translational infection research in Germany.

HIV Research in DZIF

DZIF has dedicated a special translational thematic unit (TTU) to research in the field of HIV/AIDS. TTU HIV/AIDS comprising partner sites in Bonn, Cologne, Heidelberg, Hamburg, Hanover, Langen and Munich has defined three main areas in HIV medicine, which will be addressed by DZIF researchers:

1. Prevention of HIV infection

The TTU HIV/AIDS will bring its strong basic research profile concerning innate immunity and restriction factors against HIV to the investigation of defined patient cohorts in order to identify promising targets for future preventive measures.

a. Innate and adaptive immune responses in elite controllers and acute phase HIV infection

This project has its focus on the innate immune system, where German basic and clinical research groups have strong expertise. Clinical research addressing prevention requires defined patient cohorts (e.g. elite controllers, acute phase patients), which will be developed through structural measures.

b. Enhancing and integrating international HIV research

The University of Munich has contributed to establish African HIV-patient cohorts and is involved in large international HIV prevention and treatment studies. An International Clinical Study Unit will be established to better involve German researchers into international collaborations and networks.

2. Long-term life with HIV

Translational projects will be set up to elucidate new treatment strategies for specific consequences of long term HIV-infection (and therapy), building on the strong expertise at DZIF partner sites in the areas of (i) liver damage and (ii) papillomavirus infection leading to e.g. anal cancer.

The TTU HIV/AIDS will focus on:

a. Liver injury during long-term management of HIV infection

Liver damage constitutes a common consequence of long term HIV infection and therapy and is aggravated by co-infection with hepatitis viruses. This topic will be addressed in close collaboration with the DZIF TTU on hepatitis.

b. Therapeutic vaccination of HIV infected patients against human papillomavirus (HPV)

A clinical study of a therapeutic peptide vaccine against papillomavirus infection in HIV-infected men with anal intraepithelial neoplasia (AIN) will be performed.

3. HIV cure

Early preclinical strategies to eradicate HIV infection by excision of proviral genomes from latently infected using modified Tre-recombinase cells will be translated to small animal and primate models and pave the way for later transfer into clinical application. This will be combined with analysis of the dynamics of proviral integration sites in different patient groups and depending on therapy.

To achieve its objectives for HIV cure, the TTU HIV/AIDS will focus on:

a. Characterization and excision of HIV integrates

This project builds on the strong expertise regarding analysis of lentiviral vector integration in gene therapy at the Heidelberg partner site. HIV integration site number, clonality and turnover will be monitored in defined patient populations providing essential information for all HIV eradication measures. This research is directly linked with an original approach to excise integrated HIV genomes from silently infected cells using Tre-recombinase, which was pioneered at the Hamburg partner site.

b. Strengthening preclinical HIV research

A project on eliminating viral reservoirs will be supported by capacity building in preclinical HIV research at the Heidelberg partner site including organotypic and small animal models as well as imaging under biosafety level 3 (BSL3) conditions. The gene therapy approach will be further supported by a professorship for Gene Therapy to be established in Cologne, and
research on primate models will be performed at sites in Langen and Göttingen.

4. HIV research cooperation with developing countries

While medical doctors in the northern hemisphere are now confronted with the clinical consequences of long-term infection and treatment, the focus in developing countries is on sustaining and improving therapeutic management with limited resources. Also the evaluation of vaccines against HIV and a better understanding of correlation of protection are of essential importance to our African partners.

The University of Munich has founded in 1995 the Mbeya Medical Research Programme (MMRP), which has rapidly developed to one of the most vibrant rural African research centres, with currently over 20 active clinical studies. Research activities cover the full bandwidth of basic research to clinical trials, epidemiology, operational research and intervention.

Since 2008, MMRP has been handed over to the National Institute of Medical Research and is now successively managed through Tanzanian Scientists. This is also a result of the intensive capacity development with training of 10 scientists and more than 40 technical staff members.

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