Skip to main content
OpenTrials
Completed

NCT Number: NCT04266002

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

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)

Completed

Looking for future studies?

Notify Me

Key information

Conditions

HIV-1-infection HIV Associated Neurocognitive Disorder

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hôpital d'Argenteuil, Argenteuil, France

Loading trial locations.

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Validation of Charter score for the CNS diffusion of antiretroviral drugs

Other

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 outcomes

  1. Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.

    Time frame: Change from Baseline to Week 96

    HIV associated neurocognitive disorders classification with Frascati 3-stage

Secondary outcomes

  1. Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.

    Time frame: Change from Baseline to Week 48

    HIV associated neurocognitive disorders classification with Frascati 3-stage

  2. To evaluate HIV associated neurocognitive disorders and Global Deficit Score change

    Time frame: Change from Baseline to Week 48

    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.

  3. To evaluate HIV associated neurocognitive disorders and Global Deficit Score change

    Time frame: Change from Baseline to Week 96

    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.

  4. 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

    Time frame: Change from Baseline to Week 48

    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).

  5. 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

    Time frame: Change from Baseline to Week 96

    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).

  6. To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads

    Time frame: Change from Baseline to Week 48

    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.

  7. To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads

    Time frame: Change from Baseline to Week 96

    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.

  8. To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF

    Time frame: Day 0

    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.

  9. To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF

    Time frame: Week 48

    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.

  10. To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF

    Time frame: Week 96

    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.

  11. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 12

    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

  12. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 24

    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

  13. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 36

    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

  14. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 48

    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

  15. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 60

    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

  16. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 72

    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

  17. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 84

    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

  18. To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF

    Time frame: Week 96

    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

  19. 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

    Time frame: Change from Baseline to Week 48

    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.

  20. 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

    Time frame: Change from Baseline to Week 96

    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.

  21. 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

    Time frame: Change from Baseline to Week 48

    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.

  22. 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

    Time frame: Change from Baseline to Week 96

    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.

  23. To evaluate HIV associated neurocognitive disorders and Brain MRI change

    Time frame: Change from Baseline to Week 48

    HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change

  24. To evaluate HIV associated neurocognitive disorders and Brain MRI change

    Time frame: Change from Baseline to Week 96

    HIV associated neurocognitive disorders are measured with Frascati 3-stage classification and Global Deficit Score. Brain MRI is performed before and after ARV change

  25. To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND

    Time frame: Day 0

    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.

  26. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 12

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  27. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 24

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  28. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 36

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  29. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 48

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  30. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 60

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  31. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 72

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  32. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 84

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  33. To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status

    Time frame: Change from Baseline to Week 96

    10-items Cognitive Complaint Questionnaire is altered with a cutoff ≥3

  34. 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

    Time frame: Change from Baseline to Week 12

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  35. 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

    Time frame: Change from Baseline to Week 24

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  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

    Time frame: Change from Baseline to Week 36

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  37. 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

    Time frame: Change from Baseline to Week 48

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  38. 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

    Time frame: Change from Baseline to Week 60

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  39. 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

    Time frame: Change from Baseline to Week 72

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  40. 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

    Time frame: Change from Baseline to Week 84

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  41. 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

    Time frame: Change from Baseline to Week 96

    Inventory of Activity Daily Living part II is altered with a cutoff ≥2

  42. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 12

    Quality of Life is measured by Short Form 36 Health Survey

  43. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 24

    Quality of Life is measured by Short Form 36 Health Survey

  44. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 36

    Quality of Life is measured by Short Form 36 Health Survey

  45. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 48

    Quality of Life is measured by Short Form 36 Health Survey

  46. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 60

    Quality of Life is measured by Short Form 36 Health Survey

  47. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 72

    Quality of Life is measured by Short Form 36 Health Survey

  48. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 84

    Quality of Life is measured by Short Form 36 Health Survey

  49. To evaluate the Quality of Life during the study

    Time frame: Change from Baseline to Week 96

    Quality of Life is measured by Short Form 36 Health Survey

  50. To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)

    Time frame: Change from Baseline to Week 48

    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)

  51. To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)

    Time frame: Change from Baseline to Week 96

    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)

  52. To study the incidence and severity of adverse events during the study period

    Time frame: Week 12

    Neurologic or neuropsychologic adverse events are particularly analysed

  53. To study the incidence and severity of adverse events during the study period

    Time frame: Week 24

    Neurologic or neuropsychologic adverse events are particularly analysed

  54. To study the incidence and severity of adverse events during the study period

    Time frame: Week 36

    Neurologic or neuropsychologic adverse events are particularly analysed

  55. To study the incidence and severity of adverse events during the study period

    Time frame: Week 48

    Neurologic or neuropsychologic adverse events are particularly analysed

  56. To study the incidence and severity of adverse events during the study period

    Time frame: Week 60

    Neurologic or neuropsychologic adverse events are particularly analysed

  57. To study the incidence and severity of adverse events during the study period

    Time frame: Week 72

    Neurologic or neuropsychologic adverse events are particularly analysed

  58. To study the incidence and severity of adverse events during the study period

    Time frame: Week 84

    Neurologic or neuropsychologic adverse events are particularly analysed

  59. To study the incidence and severity of adverse events during the study period

    Time frame: Week 96

    Neurologic or neuropsychologic adverse events are particularly analysed

  60. To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study

    Time frame: Day 0

    ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry

  61. To study the trough levels of antiretroviral drugs in blood after ARV change

    Time frame: Week 4

    ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry

  62. To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study

    Time frame: Week 48

    ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry

  63. To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study

    Time frame: Week 96

    ARV concentrations were determined using an ultra-performance liquid chromatography coupled with tandem mass spectrometry

  64. To study the cardiovascular risk evolution

    Time frame: Change from Baseline to Week 48

    Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score

  65. To study the cardiovascular risk evolution

    Time frame: Change from Baseline to Week 96

    Cardiovascular risk is measured with Framingham score, Systematic Coronary Risk Estimation, and D:A:D study model score are calcul

Sponsors and collaborators

Lead sponsor

Hôpital Franco-Britannique-Fondation Cognacq-Jay

Other

Collaborators

  • Hospital Ambroise Paré Paris

Registry information

Official study 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)

Important dates

Study start
2011
Primary completion
2012
Study completion
2016
First posted
Feb 12, 2020
Registry last updated
Feb 12, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.