Project

Back to overview

Longitudinal Neurocognitive Assessment in the Metabolic and Aging Cohort of the Swiss HIV Cohort Study: the NAMACO study

English title Longitudinal Neurocognitive Assessment in the Metabolic and Aging Cohort of the Swiss HIV Cohort Study: the NAMACO study
Applicant Cavassini Matthias
Number 163348
Funding scheme Project funding (special)
Research institution Service de Médecine Interne Département de Médecine CHUV
Institution of higher education University of Lausanne - LA
Main discipline Internal Medicine
Start/End 01.01.2016 - 31.12.2019
Approved amount 460'838.00
Show all

All Disciplines (2)

Discipline
Internal Medicine
Neurology, Psychiatry

Keywords (7)

HIV; neurocognitive disorders; incidence; Pharmacokinetic; risk factors; MRI; HIV associated neurocognitive disorders

Lay Summary (French)

Lead
L'infection par le VIH est devenue une maladie chronique. On constate que certains patients infectés par le VIH et bien traités peuvent malgré tout développer des troubles cognitifs (mémoire, concentration, temps de réaction). Ces troubles semblent survenir à un âge plus précoce que dans la population générale. Il est nécessaire de mieux comprendre l’étiologie de ces troubles, d’en connaître l’évolution et de développer de nouveaux moyens diagnostiques. Ce projet national multicentrique apporte sa contribution dans un suivi longitudinal
Lay summary

Contenu et objectifs du travail de recherche :

Le VIH envahit le cerveau dans les premières semaines suivant l’infection. Grâce aux traitements antirétroviraux, le spectre des maladies neurologiques causées par le VIH s’est métamorphosé. Cependant certains patients peuvent développer des troubles cognitifs classifiés comme mineurs alors que leurs répercussions fonctionnelles peuvent être majeures sur le plan personnel et professionnel. La pathogenèse de ces troubles cognitifs demeure obscure. Les hypothèses sont : une réplication du virus dans le cerveau, qui ferait office de « sanctuaire du virus », une inflammation persistante, une toxicité cérébrale de la médication anti-VIH ou une moins bonne pénétration des médicaments au niveau cérébral. Le diagnostic de ces troubles cognitifs requiert un bilan neuropsychologique complexe et exhaustif. L’étude Suisse de Cohorte VIH (www.shcs.ch) s’intéresse au vieillissement de sa population et suivra spécifiquement 1000 sujets. Ils auront 3 bilans neuropsychologiques à 2 ans d’intervalle en plus du suivi biologique habituel. Les sujets présentant des troubles cognitifs auront un bilan complémentaire en accord avec les recommandations européennes de suivi clinique des patients infectés par le VIH (www.eacsociety.org). Les buts de cette étude longitudinale sont : a) d’identifier les facteurs associés aux atteintes cognitives (et leur évolution) b) d’investiguer le rôle des taux des médicaments anti-VIH (et leurs métabolites) dans le liquide céphalo-rachidien c) d’évaluer la capacité des nouvelles analyses de séquences IRM pour le diagnostic et la prédiction du devenir des troubles cognitifs.

Contexte scientifique et social du projet de recherche :

Le projet s'inscrit au sein de l'étude de cohorte VIH suisse alors que plus de 30 % des personnes infectées par le VIH en Suisse ont plus de 50 ans. Mieux comprendre leurs "vieillissements" sur le plan cognitif est nécessaire.   

Direct link to Lay Summary Last update: 12.01.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well‐treated HIV‐positive population?
Metral M, Nadin I, Locatelli I, Tarr PE, Calmy A, Kovari H, Brugger P, Cusini A, Gutbrod K, Schmid P, Schwind M, Kunze U, Di Benedetto C, Pignatti R, Du Pasquier R, Darling KEA, Cavassini M, Cavassini Matthias, Pasquier Renaud Du, Métral Mélanie, Simioni Samanta, Brugger Peter, Gutbrod Klemens, Monsch Andreas U, et al. (2019), How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well‐treated HIV‐positive population?, in HIV Medicine, hiv.12828-hiv.12828.
Polypharmacy, Drug–Drug Interactions, and Inappropriate Drugs: New Challenges in the Aging Population With HIV
Courlet Perrine, Livio Françoise, Guidi Monia, Cavassini Matthias, Battegay Manuel, Stoeckle Marcel, Buclin Thierry, Alves Saldanha Susana, Csajka Chantal, Marzolini Catia, Decosterd Laurent, Anagnostopoulos A, Battegay M, Bernasconi E, Böni J, Braun D L, Bucher H C, Calmy A, Cavassini M, Ciuffi A, Dollenmaier G, Egger M, Elzi L, Fehr J, et al. (2019), Polypharmacy, Drug–Drug Interactions, and Inappropriate Drugs: New Challenges in the Aging Population With HIV, in Open Forum Infectious Diseases, 6(12), 1-8.
The Neurocognitive Assessment in the Metabolic and Aging Cohort ( NAMACO ) study: baseline participant profile
Métral M, Darling KEA, Locatelli I, Nadin I, Santos G, Brugger P, Kovari H, Cusini A, Gutbrod K, Tarr PE, Calmy A, Lecompte TD, Assal F, Monsch A, Kunze U, Stoeckle M, Schwind M, Schmid P, Pignatti R, Di Benedetto C, Du Pasquier R, Cavassini M, Cavassini Matthias, Du Pasquier Renaud, et al. (2019), The Neurocognitive Assessment in the Metabolic and Aging Cohort ( NAMACO ) study: baseline participant profile, in HIV Medicine, 21(1), 30-42.
The Presence of Human Immunodeficiency Virus-Associated Neurocognitive Disorders Is Associated With a Lower Adherence to Combined Antiretroviral Treatment
Kamal Susan, Locatelli Isabella, Wandeler Gilles, Sehhat Asemaneh, Bugnon Olivier, Metral Melanie, Du Pasquier Renaud, Gutbrod Klemens, Cavassini Matthias, Schneider Marie P. (2017), The Presence of Human Immunodeficiency Virus-Associated Neurocognitive Disorders Is Associated With a Lower Adherence to Combined Antiretroviral Treatment, in Open Forum Infectious Diseases, 4(2), ecoll-ecoll.

Collaboration

Group / person Country
Types of collaboration
Swiss HIV Cohort Study AND NAMACO study group Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Conference on Retroviruses and Opportunistic Infections (CROI), 2020 Individual talk Co-Moderator, neuro-HIV session: HIV is on our MINDS 08.03.2020 Boston, United States of America Cavassini Matthias;
European AIDS Clinical Society conference Poster A multi-disciplinary Neuro-HIV Platform in managing patients with neurocognitive impairment 06.11.2019 Basel, Switzerland Granziera Cristina; Du Pasquier Renaud; Darling Katharine; Nadin Isaure; Cavassini Matthias;
European AIDS Clinical Society conference Poster Central nervous system penetration of antiretroviral drugs in HIV-positive patients with neurocognitive impairment, assessed from paired plasma-CSF concentrations 06.11.2019 Basel, Switzerland Du Pasquier Renaud; Cavassini Matthias; Darling Katharine; Nadin Isaure;
HIV Glasgow conference Individual talk The effect of drug use on specific neuropsychological domains among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging COhort (NAMACO) study 28.10.2018 Glasgow, Great Britain and Northern Ireland Du Pasquier Renaud; Nadin Isaure; Cavassini Matthias;
World AIDS conference Poster The effect of alcohol consumption on specific neuropsychological testing domains in patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging COhort study (NAMACO) 23.07.2018 Amsterdam, Netherlands Cavassini Matthias; Du Pasquier Renaud; Alves Deolinda; Nadin Isaure; Vallet Yannick;
World AIDS conference Poster Neurocognitive complaints in people living with HIV: Characterizing clusters of patients with similar changes in neurocognitive complaints in the Swiss HIV Cohort Study 23.07.2018 Amsterdam, Netherlands Cavassini Matthias;
Conference on Retroviruses and Opportunistic Infections (CROI) Poster CROSS-SECTIONAL AND CUMULATIVE LONGITUDINAL CPE SCORES ARE NOT ASSOCIATED WITH HAND 04.03.2018 Boston, United States of America Metral Melanie; Nadin Isaure; Du Pasquier Renaud; Alves Deolinda; Cavassini Matthias; Vallet Yannick;
International AIDS Society conference Poster Assessing depression's impact on neurocognitive performance in the Metabolic and Ageing Cohort of the Swiss HIV Cohort Study 23.07.2017 Paris, France Nadin Isaure; Du Pasquier Renaud; Vallet Yannick; Alves Deolinda; Cavassini Matthias; Metral Melanie;
American Academy of Neurology Poster SENSITIVITY AND SPECIFICITY OF THREE SCREENING QUESTIONS FOR COGNITIVE DISORDERS 22.04.2017 Boston, United States of America Cavassini Matthias; Nadin Isaure; Metral Melanie; Du Pasquier Renaud;
CROI Poster PREVALENCE OF NEUROCOGNITIVE DISORDERS IN A WELL-TREATED AND AGING SWISS HIV-COHORT 13.02.2017 Seattle, United States of America Metral Melanie; Cavassini Matthias; Vallet Yannick; Du Pasquier Renaud; Alves Deolinda;
Challenge in Virology Talk given at a conference Neuro-HIV: where are the keys ? The key is treating the virus / The key is understanding the brain / the key is looking thoroughly at the brain 28.01.2017 Grindelwald, Switzerland Cavassini Matthias; Du Pasquier Renaud; Granziera Cristina;


Associated projects

Number Title Start Funding scheme
192777 Longitudinal analysis of the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study : Step 2 01.04.2020 Project funding (special)
148522 Swiss HIV Cohort Study (SHCS) 01.01.2014 Cohort Studies Large

Abstract

1.SUMMARY HIV infection is now a chronic disease. Although the virus can be controlled, there is accumulating evidence that aging HIV-infected patients, even those with undetectable HIV viral loads, develop neurocognitive disorders at a younger age than matched HIV-negative controls. The pathogenesis of these neurocognitive disorders remains obscure. Immune activation, HIV replication in sanctuary sites such as the central nervous system (CNS), combined Anti-Retroviral Therapy (cART) toxicity and co-morbidities are all potentially responsible. Since the advent of cART, the spectrum of neurocognitive disorders has changed. In pre-cART era, severe HIV-associated dementia (HAD) was straightforward to diagnose; post-cART, the diagnosis of mild-to-moderate neurocognitive disorders requires complex, costly and time-consuming neuropsychological evaluation. Consequently, HIV-associated neurocognitive disorders (HAND) are under-diagnosed, with consequent undesirable repercussions on patients’ personal and professional lives. As HIV-positive patients continue to age, there is a growing need for a simplified and validated set of diagnostic tools for HAND. Another challenging aspect of HAND is that we are unable to predict the long-term outcome in an individual patient. Do these patients stabilise or do they progress towards dementia? In addition, no optimal treatment for HAND has been identified to date. To answer these multiple gaps, there is an urgent need to perform a comprehensive, longitudinal study in a large cohort of aging HIV-infected patients in Switzerland. The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study was designed and spearheaded by Cavassini and Du Pasquier in 2012. It consists of 1000 patients aged over 45 years old recruited over a 3-year period (2013-2015), all of whom will have baseline standardised neuropsychological testing. In order to allow a longitudinal study, we plan to review all the patients after two (2015-2017) and four years (2017-2019). In addition, patients with HAND and a control group without HAND are being investigated further according to the European AIDS Clinical Society (EACS) guidelines, with neurological examination, cerebral imaging and a lumbar puncture with cerebrospinal fluid (CSF) collection. In this proposal, we aim:I. to study longitudinally the incidence of HAND and identify predictors of change in HAND in a cohort of 1000 participants. II.to use multi-contrast high resolution MRI approaches as a diagnostic tool and predictor of brain alterations in patients with HAND versus cognitively-normal HIV-positive patients.III. to investigate in detail the role of cART and metabolites drug levels in paired CSF/plasma samples predictive of HAND. We believe that this multi-disciplinary innovative approach will fill several important gaps: 1.It will improve our understanding of the longitudinal epidemiology of HAND and associated factors in the aging Swiss HIV-positive population that differs from other cohorts in terms of HIV treatment, demographic and co-morbidities.2.It could facilitate the diagnosis and follow up of HAND by objective and non-invasive methods using multi-contrast high resolution MRI3.It will improve our understanding of the potential CNS toxicity of cART and its role in HAND incidence and outcomeThis research proposal therefore addresses key issues in the development and diagnosis of neurocognitive disorders among aging HIV-infected patients. Beyond the current aims, this large and highly-characterised cohort population will enable further research in the form of the longitudinal assessment of new biomarkers, genetic studies and therapeutic interventional clinical trials.
-