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)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 24
- 主要终点
- Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
研究概览
简要总结
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)
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.
时间窗: Change from Baseline to Week 96
HIV associated neurocognitive disorders classification with Frascati 3-stage
次要结局
- 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(Change from Baseline to Week 96)
- To evaluate HIV associated neurocognitive disorders and Global Deficit Score change(Change from Baseline to Week 96)
- Demonstrate a significant improvement in HIV associated neurocognitive disorders after ARV intensification with increased CNS Penetration Effectiveness scoring ≥+3 and total CPE score ≥9.(Change from Baseline to Week 48)
- 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(Change from Baseline to Week 96)
- To evaluate the evolution of HIV associated neurocognitive disorders with plasma HIV-1 viral load cells, and plasma HIV-1 viral loads(Change from Baseline to Week 96)
- To compare HIV associated neurocognitive disorders in HIV-1 infected patients with detectable and undetectable viral load in CSF(Week 96)
- To evaluate the patterns of viral genotypic resistance in patients with virologic failure in blood or CSF(Week 96)
- To evaluate regular monitoring of cognitive impairment by Inventory of Activity Daily Living part II to detect at the earliest possible changes in cognitive status(Change from Baseline to Week 96)
- To evaluate the Quality of Life during the study(Change from Baseline to Week 96)
- To compare HIV associated neurocognitive disorders in patients with great CPE change ≥5 and patients with low CPE change (+3 or +4)(Change from Baseline to Week 96)
- To evaluate the evolution of HIV associated neurocognitive disorders with the evolution of markers in plasma: neopterin, neurofilament light chain (NFL), CCL2, IL6, IL8, CXCL10, soluble CD14(Change from Baseline to Week 96)
- To evaluate HIV associated neurocognitive disorders and Brain MRI change(Change from Baseline to Week 96)
- To compare sensitivity and specificity of the 2 screening tests (FAB test and Modified - HIV Dementia Scale) for the diagnosis of HAND(Day 0)
- To evaluate regular monitoring of cognitive impairment by 10-items Cognitive Complaint Questionnaire to detect at the earliest possible changes in cognitive status(Change from Baseline to Week 96)
- To study the cardiovascular risk evolution(Change from Baseline to Week 96)
- To study the incidence and severity of adverse events during the study period(Week 96)
- To study the trough levels of antiretroviral drugs in blood and cerebrospinal fluid during the study(Week 96)
- To study the trough levels of antiretroviral drugs in blood after ARV change(Week 4)
研究者
Gilles Force, MD
Study promotor
Hôpital Franco-Britannique-Fondation Cognacq-Jay