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