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HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy

Primary Purpose

HIV-1-infection, HIV Associated Neurocognitive Disorder

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Validation of Charter score for the CNS diffusion of antiretroviral drugs
Sponsored by
GCS IHFB Cognacq-Jay
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-1-infection focused on measuring CNS Penetration Effectiveness, Global Deficit Score, Cytokines, CSF Inflammation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject (male or female) with HIV-1 infection
  2. Subject is ≥ 18 years of age
  3. Subject with a plasma viral load (HIV-1 RNA) undetectable for at least one year or with minimal replication <500 copies/ml for at least one year at the inclusion date
  4. Patient with HIV-associated neurocognitive disorders : at least two ability domains, documented by performance of at least 1.0 standard deviation below the mean for age-education appropriate norms on standardized neuropsychological tests
  5. Patient is willing and able to understand and provide written informed consent prior to participation in this study

Exclusion Criteria:

  1. Subject with HIV-2 infection
  2. Subject with plasma viral load (HIV-1 RNA)> 500 copies/ml in the past year
  3. Subject with acquired impairment in cognitive functioning involving only one ability domain, or involving at least two ability domains but with performance better than 1.0 standard deviation below the mean (no evidence of potential cognitive impairment)
  4. Subject unable, according to the investigator, to meet the study requirements, including patients unable to perform cognitive tests
  5. Subject with acute intercurrent disease
  6. Patient with positive serology for HCV or HBsAg positive
  7. Subject with cognitive impairment related to another cause than HIV: other CNS infection, CNS neoplasm, cerebrovascular disease, preexisting neurologic disease or metabolic disorders, severe substance abuse, or systemic disease.
  8. Subject with a brain MRI or CSF analysis results that suggest another pathology than HIV associated neurocognitive disorder
  9. Subject requires treatment with immunomodulating agents (or may require such treatment during the two years monitoring) such as systemic corticosteroïds, interferons, interleukins, growth factor GM- CSF, or other targeted therapy that may interfere with macrophage markers of the study
  10. Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents
  11. Subject at which the initial lumbar punction can't be achieved
  12. Subject ≥65 years at the inclusion date, age with high risk of atherosclerotic disease

  13. Subject with significant depression : with a score ≥29 (or score

    ≥20 without questions 15 to 21) at Beck Depression Inventory II (1996 version), the neuropsychologist doesn't conduct the battery of cognitive tests

  14. Subject under curatorship or guardianship
  15. Subject at which the initial cerebral MRI can't be achieved

Sites / Locations

  • Hôpital d'Argenteuil
  • Hôpital Intercommunal Robert Ballanger
  • Centre Hospitalier de Bligny
  • Hôpital Mignot Centre Hospitalier de Versailles
  • Hôpital Raymond Poincaré
  • Centre Hospitalier de Gonesse
  • Institut Hospitalier Franco- Britannique
  • Centre Hospitalier Marc Jacquet
  • Centre Hospitalier René Dubois
  • Hôpital Delafontaine
  • Centre Hospitalier Intercommunal de Poissy Germain en Laye
  • Hôpital Foch

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

HIV-1 infected adult associated neurocognitiv

Arm Description

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 with Global Deficit Score and HAND classification, 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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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.
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).
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).
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.
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.
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.
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.
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.
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
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
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
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
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
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
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
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
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.
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.
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.
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.
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
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
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
To evaluate the Quality of Life during the study
Quality of Life is measured by Short Form 36 Health Survey
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)
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)
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
To study the incidence and severity of adverse events during the study period
Neurologic or neuropsychologic adverse events are particularly analysed
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
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
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
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
To study the cardiovascular risk evolution
Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score
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

Full Information

First Posted
January 24, 2020
Last Updated
February 9, 2020
Sponsor
GCS IHFB Cognacq-Jay
Collaborators
Hospital Ambroise Paré Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04266002
Brief Title
HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy
Official Title
Prospective Study in HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy in Plasma, After a Change in HIV Treatment With an Increased of CHARTER Score ≥ 3 (Total Score ≥ 9)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
November 1, 2011 (Actual)
Primary Completion Date
June 29, 2012 (Actual)
Study Completion Date
July 26, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
GCS IHFB Cognacq-Jay
Collaborators
Hospital Ambroise Paré Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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)
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1-infection, HIV Associated Neurocognitive Disorder
Keywords
CNS Penetration Effectiveness, Global Deficit Score, Cytokines, CSF Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Prospective Pilot study, open-label, multicenter in the Ile-de-France
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HIV-1 infected adult associated neurocognitiv
Arm Type
Other
Arm Description
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 with Global Deficit Score and HAND classification, 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)
Intervention Type
Other
Intervention Name(s)
Validation of Charter score for the CNS diffusion of antiretroviral drugs
Intervention Description
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.
Primary Outcome Measure Information:
Title
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
Description
HIV associated neurocognitive disorders classification with Frascati 3-stage
Time Frame
Change from Baseline to Week 96
Secondary Outcome Measure Information:
Title
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
Description
HIV associated neurocognitive disorders classification with Frascati 3-stage
Time Frame
Change from Baseline to Week 48
Title
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
Description
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
Title
To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
Description
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
Title
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
Description
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
Title
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
Description
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
Title
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
Description
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
Title
To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
Description
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
Title
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Description
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
Title
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Description
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
Title
To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
Description
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
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Title
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
Description
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
Title
To evaluate HIV associated neurocognitive disorders and Brain MRI change
Description
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
Title
To evaluate HIV associated neurocognitive disorders and Brain MRI change
Description
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
Title
To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND
Description
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
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 12
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 24
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 36
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 48
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 60
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 72
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 84
Title
To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
Description
10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3
Time Frame
Change from Baseline to Week 96
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 12
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 24
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 36
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 48
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 60
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 72
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 84
Title
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
Description
Inventory of Activity Daily Living part II is altered with a cutoff ≥2
Time Frame
Change from Baseline to Week 96
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 12
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 24
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 36
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 48
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 60
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 72
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 84
Title
To evaluate the Quality of Life during the study
Description
Quality of Life is measured by Short Form 36 Health Survey
Time Frame
Change from Baseline to Week 96
Title
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
Description
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
Title
To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
Description
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
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 12
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 24
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 36
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 48
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 60
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 72
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 84
Title
To study the incidence and severity of adverse events during the study period
Description
Neurologic or neuropsychologic adverse events are particularly analysed
Time Frame
Week 96
Title
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
Description
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time Frame
Day 0
Title
To study the trough levels of antiretroviral drugs in blood after ARV change
Description
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time Frame
Week 4
Title
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
Description
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time Frame
Week 48
Title
To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
Description
ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry
Time Frame
Week 96
Title
To study the cardiovascular risk evolution
Description
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
Title
To study the cardiovascular risk evolution
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject (male or female) with HIV-1 infection Subject is ≥ 18 years of age Subject with a plasma viral load (HIV-1 RNA) undetectable for at least one year or with minimal replication <500 copies/ml for at least one year at the inclusion date Patient with HIV-associated neurocognitive disorders : at least two ability domains, documented by performance of at least 1.0 standard deviation below the mean for age-education appropriate norms on standardized neuropsychological tests Patient is willing and able to understand and provide written informed consent prior to participation in this study Exclusion Criteria: Subject with HIV-2 infection Subject with plasma viral load (HIV-1 RNA)> 500 copies/ml in the past year Subject with acquired impairment in cognitive functioning involving only one ability domain, or involving at least two ability domains but with performance better than 1.0 standard deviation below the mean (no evidence of potential cognitive impairment) Subject unable, according to the investigator, to meet the study requirements, including patients unable to perform cognitive tests Subject with acute intercurrent disease Patient with positive serology for HCV or HBsAg positive Subject with cognitive impairment related to another cause than HIV: other CNS infection, CNS neoplasm, cerebrovascular disease, preexisting neurologic disease or metabolic disorders, severe substance abuse, or systemic disease. Subject with a brain MRI or CSF analysis results that suggest another pathology than HIV associated neurocognitive disorder Subject requires treatment with immunomodulating agents (or may require such treatment during the two years monitoring) such as systemic corticosteroïds, interferons, interleukins, growth factor GM- CSF, or other targeted therapy that may interfere with macrophage markers of the study Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents Subject at which the initial lumbar punction can't be achieved Subject ≥65 years at the inclusion date, age with high risk of atherosclerotic disease Subject with significant depression : with a score ≥29 (or score ≥20 without questions 15 to 21) at Beck Depression Inventory II (1996 version), the neuropsychologist doesn't conduct the battery of cognitive tests Subject under curatorship or guardianship Subject at which the initial cerebral MRI can't be achieved
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe AEGERTER
Organizational Affiliation
Clinical Research Unit
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital d'Argenteuil
City
Argenteuil
ZIP/Postal Code
95100
Country
France
Facility Name
Hôpital Intercommunal Robert Ballanger
City
Aulnay-sous-Bois
ZIP/Postal Code
93602
Country
France
Facility Name
Centre Hospitalier de Bligny
City
Briis-sous-Forges
ZIP/Postal Code
91640
Country
France
Facility Name
Hôpital Mignot Centre Hospitalier de Versailles
City
Chesnay
ZIP/Postal Code
78150
Country
France
Facility Name
Hôpital Raymond Poincaré
City
Garches
ZIP/Postal Code
92380
Country
France
Facility Name
Centre Hospitalier de Gonesse
City
Gonesse
ZIP/Postal Code
95500
Country
France
Facility Name
Institut Hospitalier Franco- Britannique
City
Levallois-Perret
ZIP/Postal Code
92300
Country
France
Facility Name
Centre Hospitalier Marc Jacquet
City
Melun
ZIP/Postal Code
77000
Country
France
Facility Name
Centre Hospitalier René Dubois
City
Pontoise
ZIP/Postal Code
95300
Country
France
Facility Name
Hôpital Delafontaine
City
Saint-Denis
ZIP/Postal Code
93200
Country
France
Facility Name
Centre Hospitalier Intercommunal de Poissy Germain en Laye
City
Saint-Germain-en-Laye
ZIP/Postal Code
78100
Country
France
Facility Name
Hôpital Foch
City
Suresnes
ZIP/Postal Code
92150
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

HIV-1 Infected Adult Subjects With HIV-associated Neurocognitive Disorders Despite Effective Antiretroviral Therapy

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