Prospective study in HIV-1 infected adult subjects with HIV-associated neurocognitive disorders despite effective antiretroviral therapy in plasma for more than one year, analyzing the evolution of cognitive disorders and markers of macrophagic inflammation in blood and cerebrospinal fluid, after a change in HIV treatment with an increased of the new scale CHARTER score ≥ 3 (total treatment score to be ≥ 9)
Neurocognitive disorders are measured using Frascati 3-stage classification and Global Deficit Score, after the following 10 standardized battery test: Grooved Pegboard for dominant and non-dominant hand, Grefex Verbal Fluency, California Verbal Learning Test (CVLT), Digit Span Wechsler Adult Intelligence Scale III, modified Paced Auditory Serial Addition Test (60 items), WAIS III Digit Symbol Test, Trail Making Test A\&B, recall of CVLT and Wisconsin Card Sorting Test; and after the Beck Depression Inventory II (BDI), Inventory of Activity Daily Living part II (IADL) and 10-items Cognitive Complaint Questionnaire (CCQ). The global CNS Penetration Effectiveness (CPE) score of ARV treatment are the sum of the scores of each ARV the patient received, according to the last published scoring. For each drug class, we considered treatment intensification only for drugs with CPE score reaching at least 3 (no intensification if switch in same drug class with same CPE score). CPE score was corrected by drugs resistance status, using cumulative genotype interpreted with the 2012 ANRS algorithm (www.hivfrenchresistance.org; v.2012) at inclusion (CPE=0 if resistance).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
IHFB001 (Neuroplustrois) is a pilot study, phase IV, open-label, multicenter in Ile-de-France region, trying to demonstrate the improvement of cognitive change after treatment characterized by its better diffusion in the central nervous system. The characteristics of the change in treatment are (Cn - Ci) ≥ 3 and Cn ≥ 9, where Cn is the Charter score of the new treatment and Ci the Charter score of the initial treatment.
Hôpital d'Argenteuil
Argenteuil, France
Hôpital Intercommunal Robert Ballanger
Aulnay-sous-Bois, France
Centre Hospitalier de Bligny
Briis-sous-Forges, France
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
HIV associated neurocognitive disorders classification with Frascati 3-stage
Time frame: Change from Baseline to Week 96
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
HIV associated neurocognitive disorders classification with Frascati 3-stage
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification. Global Deficit Score (from 0 with no deficit to 5 with high neurocognitive disorder) is calculated with the results of 10 standardized battery tests.
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification. Global Deficit Score (from 0 with no deficit to 5 with high neurocognitive disorder) is calculated with the results of 10 standardized battery tests.
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CD4 and CD8 cells are measured in plasma with flow cytometry (results in cells/µL).
Time frame: Change from Baseline to Week 48
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Hôpital Mignot Centre Hospitalier de Versailles
Chesnay, France
Hôpital Raymond Poincaré
Garches, France
Centre Hospitalier de Gonesse
Gonesse, France
Institut Hospitalier Franco- Britannique
Levallois-Perret, France
Centre Hospitalier Marc Jacquet
Melun, France
Centre Hospitalier René Dubois
Pontoise, France
Hôpital Delafontaine
Saint-Denis, France
...and 2 more locations
To evaluate the evolution of HIV associated neurocognitive disorders with changes in CD4 and CD8 cells in plasma cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CD4 and CD8 cells are measured in plasma with flow cytometry (results in cells/µL).
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma HIV-1 viral load will be measured with an ultra-sensitive technique with a threshold of 5 copies/mL.
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma HIV-1 viral load will be measured with an ultra-sensitive technique with a threshold of 5 copies/mL.
Time frame: Change from Baseline to Week 96
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result \>5 copies/mL with ultrasensitive HIV-RNA measure.
Time frame: Day 0
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result \>5 copies/mL with ultrasensitive HIV-RNA measure.
Time frame: Week 48
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score.Detectable viral load in CSF is defined as a result \>5 copies/mL with ultrasensitive HIV-RNA measure.
Time frame: Week 96
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 12
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 24
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 36
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 48
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 60
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 72
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 84
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Virologic failure in the blood is defined as two results \>100 copies/mL within one month. Virologic failure in the CSF is defined as a result \>100 copies/mL
Time frame: Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CSF biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in CSF: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CSF biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Time frame: Change from Baseline to Week 96
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Time frame: Change from Baseline to Week 48
To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Plasma biomarkers were obtained using high-performance liquid chromatography coupled with fluorimetric detection for neopterin (nmol/L), using the Quanterix® single molecule array platform for neurofilament light protein (NF-L)(pg/mL), chemokine (C-C-motif) ligand-2 (CCL2)(pg/mL), interleukine 6 (IL6)(pg/mL), interleukine 8 (IL8)(pg/mL), chemokine (C-X-C-motif) ligand-10 (CXCL10)(pg/mL), and using an enzyme-linked immunosorbent assay (Biotechne®) for soluble CD14 (sCD14)(µg/mL) levels.
Time frame: Change from Baseline to Week 96
To evaluate HIV associated neurocognitive disorders and Brain MRI change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change
Time frame: Change from Baseline to Week 48
To evaluate HIV associated neurocognitive disorders and Brain MRI change
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change
Time frame: Change from Baseline to Week 96
To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Altered Frontal Assessment Battery test is defined with a score ≤15/18 and altered modified-HIV Dementia Scale screening test is defined with a score ≤10/12.
Time frame: Day 0
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 84
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time frame: Change from Baseline to Week 96
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 12
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 24
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 36
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 48
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 60
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 72
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 84
To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time frame: Change from Baseline to Week 96
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 12
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 24
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 36
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 48
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 60
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 72
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 84
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
Time frame: Change from Baseline to Week 96
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CPE changes are analysed with most recent genotypic algorithm (v.2016)
Time frame: Change from Baseline to Week 48
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. CPE changes are analysed with most recent genotypic algorithm (v.2016)
Time frame: Change from Baseline to Week 96
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 12
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 24
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 36
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 48
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 60
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 72
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 84
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
Time frame: Week 96
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time frame: Day 0
To study the trough levels of antiretroviral drugs in blood after ARV change
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time frame: Week 4
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time frame: Week 48
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time frame: Week 96
To study the cardiovascular risk evolution
Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score
Time frame: Change from Baseline to Week 48
To study the cardiovascular risk evolution
Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score are calcul
Time frame: Change from Baseline to Week 96