RESEARCH ACTIVITY

_Laboratory for the Molecular Diagnosis of Infections Diseases (LDMDI)  – Presentation 

The mission of the LDMDI (head: Professor Emília Valadas) is to promote and develop clinical and translational research in infectious diseases. Located in Santa Maria Hospital,it is associated with the University Clinic of Infectious and Parasitic Diseases, Faculty of Medicine of the University of Lisbon. Clinical Research at the LDMDI began with the study of Mycobacterium tuberculosis latent infection using the ELISPOT assay to determine the production of interferon-gamma in response to ESAT-6 and CFP-10. Determining the serum levels of antiretroviral drugs using HPLC has also been done since 2006. These two research strands continue and are now evolving to other techniques and to the development of in-house tests.

Pharmacogenetics is a new research strand conducted at the LDMDI, in collaboration with the Faculty of Pharmacy of the University of Lisbon and with the Egas Moniz Higher College of Health. Studies on cell immunity in tuberculosis will start later this year, related to particular aspects, namely HIV infection, the role of vitamin D and of its receptor’s polymorphism in the capacity of monocytes-derived macrophages to destroy mycobacteria. This research strand stems from Professor Emília Valadas’ PhD thesis on immunity in tuberculosis conducted at the London School of Hygiene & Tropical Medicine. Contacts with that institution are a great asset to the design of joint projects.

The close collaboration between LDMDI and physicians of the Infectious Diseases Service of HSM has been crucial to the quality of the work performed. A few master degree theses (Master Degree in Emerging Infectious Diseases, FML) and internships for students from other faculties of medicine (FM of the University of the Algarve) have also been conducted at the LDMDI.

_Research and Integrated Treatment of HIV/AIDs and Hepatitis Unit (created in 2011, by dispatch of the Board of Santa Maria Hospital)

_International Networks (University Clinic of Infectious and Parasitic Diseases and Santa Maria Hospital)
_ NEAT (European AIDS Treatment Network) – Sixth Framework Program 6 (FP6) – Partner 7 (FML)
_ NEAT (European AIDS Treatment Network) – NEAT001/ANRS143 trial – ensaio clínico – Hospital de Santa Maria (Coordenador Nacional – Francisco Antunes)

NEAT (European AIDS Treatment Network) – Sixth Framework Program 6 (FP6) – Partner 7 (FML)

NEAT is a network of excellence funded by the European Commission. Its mission is to strengthen Europe’s capacity for HIV clinical research. Its main activities are centred on clinical research (clinical study NEAT 001/ANRS143 HIV and subsidiary studies, the NEAT Hep C/HIV Cohort Network and activities related to training and education.

The Faculty of Medicine of the University of Lisbon (institution 7) is a partner of NEAT. The third postgraduate course on Drug Therapy in HIV infection/AIDS was funded by NEAT, and the Infectious Diseases Service is the National Coordinating Centre of the clinical study NEAT001 and 11 patients were included.

_ EuroSIDA – observational study funded by the European Union (National Coordinator – Francisco Antunes)

EuroSIDA is a prospective observational cohort study of over 16.505 patients monitored in 103 hospitals from 32 European countries, Israel and Argentina. The main purpose of the study is to have access to the impact of antiretrovirals on HIV-infected population living in Europe.

EuroSIDA is funded by the European Union through the BIOMED 1-2, 5th, 6th, and 7th Framework programmes and EuroCoord. In addition to these funds, it received donations from Gilead, Pfizer, BMS, and Merk. The Infectious Diseases Services is the National Coordinator and has 186 patients.

_ INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) – set up in 2006 by the National Institute of Allergy and Infectious Diseases, funded by the University of Minnesota (USA)
_ START (Strategic Timing of AntiRetroviral Therapy) – clinical trial – Santa Maria Hospital (National Coordinator – Francisco Antunes)

_ Other International and national collaboration (responsible Professor Emília Valadas)

ACHIEV2E Collaboration Study Group – started in 2005; it encompasses 12 European centres and one in Africa. Its main objectives are: to assess the response of HIV2 infected patients to antiretroviral treatment, study the natural history of HIV2 infection, determine HIV2 resistance mutations, and prepare international recommendations on the treatment of this infection.

The International HIV Controllers Study is an international study organized by Professor Bruce Walker which brings together several organizations: Massachusetts General Hospital, The Broad Institute of Harvard and MIT, Harvard Medical School, The Ragon Institute of MGH, MIT, and Harvard, SAIC-Frederick, University of KwaZulu-Natal, and University of California, San Francisco. It includes HIV infected patients who, without therapy, can keep low “viral loads”. The main objectives include; to create an international cohort of HIV1 infected persons who can control de infection without resorting to medication; to determine the influence of genetic factors in the control of infection; to define which are innate and adaptive responses in those individuals; to describe the patterns of viral evolution in situations where there is control of infection; to ascertain the contribution of viral fitness in the control of infection.

The Portuguese HIV-2 Study Group is an international study on HIV2 infection, organized by Dr. Ricardo Camacho, from Egas Moniz Hospital, CHLO. Its main objective is to determine which mutations confer HIV2 resistance to antiretrovirals.

The Portuguese Study Group of Co-Infection (GEPCOI) studies viral hepatitis in its various aspects, from epidemiology to treatment. It includes data from most Portuguese hospitals.

Other Projects (responsible Professor Emília Valadas)

2010-2012: HIVCONTROL – Control based on dynamic modelling of HIV-1 infection for therapy design. Foundation for Science and Technology. PTDC/EEA-CRO/100128/2008. In collaboration with the Institute of Systems and Computer Engineering, Research and Development in Lisbon (INESC ID/INESC/IST/UTL).

2010-2012: Characterization and genotyping of Portuguese strains of Francisella tularensis. Foundation for Science and Technology. PTDC/SAU-ESA/104947/2008. In collaboration with the National Health Institute Doctor Ricardo Jorge.
2009/2012: Does malaria increase susceptibility to tuberculosis? The role of malaria-pigment induced immune-suppression. Foundation for Science and Technology. PIC/IC/83214/2007. In collaboration with the Institute of Molecular Medicine, Faculty of Medicine of Lisbon.

2010/2012: Strategies for early detection of renal failure in patients with HIV infection: the new troponin. Funded by ViiV Healthcare.

2010-2012: Diagnosis of Mycobacterium tuberculosis infection in individuals infected with human immunodeficiency virus. Funded by Gilead Sciences.

2012: Evaluation of Mycobacterium tuberculosis infection in patients with kidney disease. In collaboration with Santa Marta Hospital, Lisbon. Master Degree Dissertation (Master Degree in Emerging Infectious Diseases, FML) (Dr. João Furtado).

2012: Toxoplasma gondii infection in schizophrenics followed at HSM/CHLN. Master Degree Dissertation (Master Degree in Emerging Infectious Diseases, FML) (Dr. João Anastácio).

2012-2013: Assessment of cardiovascular risk in HIV1 infected patients. PhD thesis, FML (Dr. António Pais Lacerda).

Projects (responsible Robert Badura)

2011-2013: Cytotoxic activity of TCD8+ cells in patients infected with HIV1 under antiretroviral therapy and with a CD4/CD8 ratio higher than one. Funded by the Portuguese Society of Infectious Diseases and Clinical Microbiology.

2011-2013: Immunological and virological characterization of HIV.1 infected patients undergoing antiretroviral therapy at the time of seroconversion. In collaboration with the Institute of Molecular Medicine. Funded by ViiV Healthcare and Gilead Sciences

Projects (responsible João Paulo Cruz)

2010-2012: GENOFARM, impact of pharmacogenetics in the population pharmacokinetics of antiretroviral agents in patients co-infected with HIV and HBV and/or HCV. PhD thesis, FF, UL (Dr. João Paulo Cruz).

2011-2013: Impact of inter –subject pharmacokinetic variability and genotypic inhibitory quotient in the effectiveness of darunavir in HIV-1 infected patients. Master Degree Dissertation, FML (Dr. Cristina Carvalho).

2012-2014: Relationship between the therapeutic efficacy and plasma concentration of ribavirin in chronic hepatitis C. In collaboration with the Gastroenterology Service of HSM (Professor Rui Marinho).