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Opportunistic Infections in the Era of combination ART: Collaborative Analysis of European HIV Cohort Studies

English title Opportunistic Infections in the Era of combination ART: Collaborative Analysis of European HIV Cohort Studies
Applicant Furrer Hansjakob
Number 149792
Funding scheme Project funding (special)
Research institution Klinik und Poliklinik für Infektiologie Inselspital
Institution of higher education University of Berne - BE
Main discipline Internal Medicine
Start/End 01.11.2013 - 31.10.2017
Approved amount 488'500.00
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All Disciplines (3)

Discipline
Internal Medicine
Infectious Diseases
Clinical Immunology and Immunopathology

Keywords (8)

HIV-Infection; Tuberculosis; Opportunistic Infections; HIV Replication; Antiretroviral Therapy; Immune-Resconstitution; Prophylaxis of Opportunistic Infections; Swiss HIV Cohort Study

Lay Summary (German)

Lead
HIV-infizierte Menschen entwickeln eine schwerste Abwehrschwäche (AIDS) und sterben an opportunistischen Infektionen. Dank der antiretroviralen Therapie können HIV-Infizierte ihr Abwehrsystem wieder aufbauen und ein nahezu normales Leben führen. Bei einem Teil wird die HIV-Infektion aber erst entdeckt, wenn sie an opportunistischen Infektionen erkrankt sind. Bei solchen Menschen werden wir den Krankheitsverlauf unter Behandlung untersuchen, damit wir sie in Zukunft optimal betreuen können.
Lay summary

Inhalt und Ziel des Forschungsprojekts

Bei rund einem Fünftel der HIV-infizierten Menschen verläuftdie Infektion unerkannt, bis sie in schwerster Abwehrschwäche anopportunistischen Infektionen erkranken. Diese Infektionen müssen mitAntibiotika über Jahre behandelt werden, bis sich das Abwehrsystem unterantiretroviraler Therapie (ART) erholt. Eine durchgemachte opportunistischeInfektion dürfte den Heilungsverlauf unter ART beeinträchtigen. Diesuntersuchen wir, mit der COHERE Datenbank. Sie ist die grösste Datenbank HIVinfizierter Menschen und erlaubt, auch relativ seltene Ereignisse zuanalysieren.

Unsere Fragestellungen:

1.     Was ist der Einfluss opportunistischer Infektionen auf den Behandlungserfolg der ART?

2.     Haben AIDS Patienten, welche an einer Tuberkuloseerkranken, ein höherer Risiko für andere opportunistische Infektionen?

3.     Was beeinflusst das Risiko, an einer Tuberkulose zu erkranken?Spielt die Vermehrung von HI-Viren auch eine wichtige Rolle?

4.     Unter welchen Bedingungen können Antibiotika zurBehandlung der opportunistischen Infektionen abgesetzt werden?

 

Wissenschaftlicherund gesellschaftlicher Kontext des Forschungsprojekts

Mit unserer Forschung wird es uns gelingen, denKrankheitsverlauf von AIDS Patienten mit opportunistischen Infektion besser zuverstehen und sie gezielter behandeln zu können. Ergebnisse unserer Forschungüber die Tuberkulose bei HIV-Infektion sind für stark betroffene Länder, z.B. inAfrika, wichtig.

Direct link to Lay Summary Last update: 22.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Long-term immune response to yellow fever vaccination in HIV-infected individuals depends on HIV-RNA suppression status: Implications for vaccination schedule.
Veit Olivia, Domingo Cristina, Niedrig Matthias, Staehelin Cornelia, Sonderegger Beat, Delphine Héquet, Stoeckle Marcel, Calmy Alexandra, Schiffer Veronique, Bernasconi Enos, Flury Domenica, Hatz Christoph, Zwahlen Marcel, Furrer Hansjakob, Furrer Hansjakob (2017), Long-term immune response to yellow fever vaccination in HIV-infected individuals depends on HIV-RNA suppression status: Implications for vaccination schedule., in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies.
Fenner Lukas, Atkinson Andrew, Boulle Andrew, Fox Matthew P, Prozesky Hans, Zürcher Kathrin, Ballif Marie, Furrer Hansjakob, Zwahlen Marcel, Davies Mary-Ann, Egger Matthias, Egger Matthias (2017), HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies., in Journal of the International AIDS Society, 20(1), 21327-21327.
Opportunistic Diseases During HIV Infection-Things Aren't What They Used to Be, or Are They?
Furrer Hansjakob (2016), Opportunistic Diseases During HIV Infection-Things Aren't What They Used to Be, or Are They?, in The Journal of infectious diseases, 214(6), 830-1.
AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be.
Gisler Valentin, Kraus David, Nemeth Johannes, Lecompte Marthe Than, Merz Laurent, Stoeckle Marcel, Schmid Patrick, Bernasconi Enos, Weber Rainer, Cavassini Matthias, Calmy Alexandra, Elzi Luigia, Furrer Hansjakob (2014), AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be., in Journal of the International AIDS Society, 17(4 Suppl 3), 19621-19621.

Collaboration

Group / person Country
Types of collaboration
Swiss HIV Cohort Study Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
21th International Workshop on HIV Observational Databases (IWHOD) 2017 Talk given at a conference Prevalent tuberculosis at ART start associated with mortality and risk of opportunistic diseases, but not always - the COHERE network 30.03.2017 Lissabon, Portugal Atkinson Andrew; Furrer Hansjakob;
20th International Workshop on HIV Observational Databases (IWHOD) 2016 Individual talk HIV-replication as independent risk factor for primary and secondary CMV-retinitis, extrapulmonal cryptococcosis and disseminated M.avium disease 07.04.2016 Budapest, Hungary Atkinson Andrew; Furrer Hansjakob;
Conference on Retroviruses and Opportunistic Infections (CROI) 2016 Poster Association of tuberculosis with CD4 recovery and HIV RNA decline on ART in Europe 22.02.2016 Boston, United States of America Atkinson Andrew; Furrer Hansjakob; Zwahlen Marcel;
15th Conference of the European AIDS Clinical Society (EACS) 2015 Individual talk HIV viral load as an independent risk factor for tuberculosis: the COHERE collaboration. 21.10.2015 Barcelona, Spain Fenner Lukas; Atkinson Andrew; Kraus David; Zwahlen Marcel; Furrer Hansjakob;
15th Conference of the European AIDS Clinical Society (EACS) 2015 Poster HIV replication is a major predictor of primary and recurrent Pneumocystis pneumonia - Implications for prophylaxis recommendations. 21.10.2015 Barcelona, Spain Kraus David; Gisler Valentin; Furrer Hansjakob;
15th Conference of the European AIDS Clinical Society (EACS) 2015 Individual talk AIDS defining opportunistic diseases in the Swiss HIV Cohort Study: A comprehensive review 1988-2013 21.10.2015 Barcelona, Spain Atkinson Andrew; Furrer Hansjakob; Gisler Valentin; Kraus David;
19th International Workshop on HIV Observational Databases 2015 Talk given at a conference Secondary PcP prophylaxis can be safely withdrawn in patients with CD4 counts of 100-200 c/!L and suppressed HIV-RNA 26.03.2015 Catania, Italy Furrer Hansjakob; Kraus David;
HIV Drug Therapy Glasgow Congress 2014 Poster AIDS defining opportunistic infections in patients with high CD4 counts in the combination antiretroviral therapy (cART) era: things ain't what they used to be 02.11.2014 Glasgow, Great Britain and Northern Ireland Furrer Hansjakob; Gisler Valentin;


Associated projects

Number Title Start Funding scheme
134277 Swiss HIV Cohort Study (SHCS) 01.01.2011 Cohort Studies Large

Abstract

Opportunistic Infections in the Era of combination ART:Collaborative Analysis of European HIV Cohort Studies1.Summary of the Research PlanThe advent of combination antiretroviral therapy (cART) after 1996 has changed the epidemiology of opportunistic illnesses (OI) in HIV-infection substantially. cART suppresses HIV replication and leads to a marked reconstitution of immune-competence of which the CD4 lymphocyte count in peripheral blood is the classical marker. HIV-infected patients without prior OI have now a very low risk of acquiring classical HIV-associated infections, cART associated immune-reconstitution being the most potent prophylaxis against OIs.However, even in resource rich countries, a high proportion of HIV-infected persons present to clinical care in late stages of their disease with low CD4 in up to 10-20% with symptoms of an OI. In this patient group we cannot prevent a first OI. However, early start of cART still reconstitutes immune functions in these AIDS patients. These patients can stop their maintenance antimicrobial treatment against the indicator OI if they reach sustained increase of their CD4 count above defined levels. However, these levels are defined by expert panels based on data of the early cART era.Active tuberculosis (TB) as an OI in HIV Infection needs special emphasis, because TB is the most frequent OI worldwide with the highest impact on morbidity and mortality, and because even HIV-infected persons with high CD4 counts are at much higher risk of TB than HIV-negatives.We aim to address the hitherto unanswered questions:Is a history of a specific OI associated with a lesser virological, immunological or clinical response to cART and has this OI an influence on survival?Is pulmonary TB before starting cART associated with specific OIs during follow-up?Is suppression of HIV replication by cART independently of CD4 count associated with a better immune-competence against OIs?- Are the guidelines on secondary antimicrobial prophylaxis of OIs too conservative because they do not take into account viral suppression as a marker of immune-competence- Is the incidence of TB significantly lower in patients with high CD4 counts if HIV replication is suppressedSince the incidence of OIs is low in Europe, databases of single country cohorts are unlikely to be able to answer this issues. Therefore, we aim to address these question in the pan-European database of Collaboration of Observational HIV Epidemiological Research Europe (COHERE). COHERE is a collaboration of 36 European HIV cohorts, includes about 250’000 HIV-infected patients and is largest collaboration of HIV cohort studies worldwide (http://etudes.isped.u-bordeaux2.fr/cohere/). The main applicant of this project is the co-leader of the research group on opportunistic infection in COHERE.
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