Clinical trial NCT04266002: 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
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1-infection
HIV Associated Neurocognitive Disorder
Keywords: CNS Penetration Effectiveness
Global Deficit Score
Cytokines
CSF Inflammation
Lead sponsor: Hôpital Franco-Britannique-Fondation Cognacq-Jay
Sponsor class: OTHER
Collaborators: name: Hospital Ambroise Paré Paris
First posted: 2020-02-12
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective Pilot study, open-label, multicenter in the Ile-de-France
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
timeFrame: Change from Baseline to Week 96
Secondary outcomes:
measure: Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
timeFrame: Change from Baseline to Week 48
measure: To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
timeFrame: Change from Baseline to Week 48
measure: To evaluate HIV associated neurocognitive disorders and Global Deficit Score change
timeFrame: Change from Baseline to Week 96
measure: 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
timeFrame: Change from Baseline to Week 48
measure: 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
timeFrame: Change from Baseline to Week 96
measure: To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
timeFrame: Change from Baseline to Week 48
measure: To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads
timeFrame: Change from Baseline to Week 96
measure: To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
timeFrame: Day 0
measure: To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
timeFrame: Week 48
measure: To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF
timeFrame: Week 96
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 12
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 24
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 36
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 48
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 60
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 72
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 84
measure: To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF
timeFrame: Week 96
measure: 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
timeFrame: Change from Baseline to Week 48
measure: 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
timeFrame: Change from Baseline to Week 96
measure: 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
timeFrame: Change from Baseline to Week 48
measure: 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
timeFrame: Change from Baseline to Week 96
measure: To evaluate HIV associated neurocognitive disorders and Brain MRI change
timeFrame: Change from Baseline to Week 48
measure: To evaluate HIV associated neurocognitive disorders and Brain MRI change
timeFrame: Change from Baseline to Week 96
measure: To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND
timeFrame: Day 0
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 12
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 24
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 36
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 48
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 60
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 72
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 84
measure: To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status
timeFrame: Change from Baseline to Week 96
measure: 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
timeFrame: Change from Baseline to Week 12
measure: 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
timeFrame: Change from Baseline to Week 24
measure: 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
timeFrame: Change from Baseline to Week 36
measure: 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
timeFrame: Change from Baseline to Week 48
measure: 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
timeFrame: Change from Baseline to Week 60
measure: 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
timeFrame: Change from Baseline to Week 72
measure: 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
timeFrame: Change from Baseline to Week 84
measure: 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
timeFrame: Change from Baseline to Week 96
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 12
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 24
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 36
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 48
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 60
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 72
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 84
measure: To evaluate the Quality of Life during the study
timeFrame: Change from Baseline to Week 96
measure: To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
timeFrame: Change from Baseline to Week 48
measure: To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)
timeFrame: Change from Baseline to Week 96
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 12
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 24
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 36
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 48
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 60
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 72
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 84
measure: To study the incidence and severity of adverse events during the study period
timeFrame: Week 96
measure: To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
timeFrame: Day 0
measure: To study the trough levels of antiretroviral drugs in blood after ARV change
timeFrame: Week 4
measure: To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
timeFrame: Week 48
measure: To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study
timeFrame: Week 96
measure: To study the cardiovascular risk evolution
timeFrame: Change from Baseline to Week 48
measure: To study the cardiovascular risk evolution
timeFrame: Change from Baseline to Week 96
Other outcomes:
Locations:
city: Argenteuil
country: France
facility: Hôpital d'Argenteuil
city: Aulnay-sous-Bois
country: France
facility: Hôpital Intercommunal Robert Ballanger
city: Briis-sous-Forges
country: France
facility: Centre Hospitalier de Bligny
city: Chesnay
country: France
facility: Hôpital Mignot Centre Hospitalier de Versailles
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Gonesse
country: France
facility: Centre Hospitalier de Gonesse
city: Levallois-Perret
country: France
facility: Institut Hospitalier Franco- Britannique
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Pontoise
country: France
facility: Centre Hospitalier René Dubois
city: Saint-Denis
country: France
facility: Hôpital Delafontaine
city: Saint-Germain-en-Laye
country: France
facility: Centre Hospitalier Intercommunal de Poissy Germain en Laye
city: Suresnes
country: France
facility: Hôpital Foch
Study officials:
affiliation: Clinical Research Unit
name: Philippe AEGERTER
role: STUDY_DIRECTOR
References: