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

Hôpital Franco-Britannique-Fondation Cognacq-Jay

Status: Completed

Conditions: HIV-1-infection; HIV Associated Neurocognitive Disorder

Treatments: Other: Validation of Charter score for the CNS diffusion of antiretroviral drugs

Study type: Interventional

Funder types: Other

Identifiers

NCT04266002

IHFB001

Details and patient eligibility

About

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)

Full 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).

Enrollment: 31 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

HIV-1 infected adult associated neurocognitiv

Other group

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)

Treatment:

Other: Validation of Charter score for the CNS diffusion of antiretroviral drugs