Study to Assess the ART Impact on the Brain Outcomes. The ARBRE Study

Study Overview
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Brief Summary
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The ARBRE Study is an observational prospective trial aimed at investigating the impact of the therapy initiation with INTIs on brain outcomes according to the time of therapy initiation. Three study arms are considered: 1) Early treated HIV-1 infected patients (<3 months since estimated date of infection), 2) Regularly treated HIV-1 infected patients (>6 months since estimated date of infection), 3) Matched seronegative control group. Study assessments will be performed at baseline, 1 month and 12 months. Study assessments will comprise comprehensive evaluation of brain outcomes. They will include cognitive functioning, neuroimaging parameters, and functional outcomes.

Detailed Description
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Randomized patients will receive LA CAB+RPV administration in the hospital (standard of care) or out-of- hospital administration every 2 months (M2, M4, M6, M8,M10, M12). Medical visits, rutinary blood tests and pharmacy visits at the hospital of reference will take place every 6 months- at baseline, M1 (if patient has not previously receiving LA CAB+RPV), M6 and M12.

Official Title
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Observational Prospective Trial to Investigate the Impact of Antiretroviral Therapy Initiation With Integrase Strand Transfer Inhibitors on Brain Outcomes:The ARBRE Study:Impact of AntiRetroviral Therapy With INSTI on BRain outcomEs (ARBRE) According to the Time of Therapy Initation

Conditions
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HIV-1 Infection, Cognitive Impairment

Participation Criteria
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Eligibility Criteria
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The study criteria for participation in the study will be the following: Inclusion Criteria: Age 18-65 years old Voluntary participation. Signed written consent. Confirmed HIV-1 infection (for arms A and B). Intention to initiate therapy with cART containing an INSTI. Specifically, the regimen included raltegravir, elvitegravir or dolutegravir. Exclusion Criteria: Prior diagnosis of opportunistic infection involving CNS. Current diagnosis of psychiatric disorder. Current or past diagnosis of neurologic disease. Inability to develop any of the tasks required for the study. Pregnancy. History of suboptimal adherence (for arms A and B).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Early treated patients<br>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy presenting recent HIV-1 infection. Recent HIV-1 infection was defined as having a positive plasma viral load and/or p24 antigen with a negative ELISA or having a positive ELISA and undetermined Western-Blot, or having a positive ELISA and absence of p31 antigen in a positive Western-Blot, or seroconversion ELISA in less than 3 months. | |
| Regularly treated patients<br>Patients with confirmed HIV-1 infection attended in the HIV Unit of the Hospital Universitari Germans Trias i Pujol who initiated therapy, did not fulfil the criteria for recent HIV-1 infection, and had an estimated time >6 months reported by the patient and/or by the responsible physician since HIV transmission. | |
| Seronegative volunteers<br>HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Global Cognitive Functioning | The measure used will be NPZ-12 (NeuroPsychological Z-12). Minimum value: -5 Maximum value: +5. Mean: 0. Lower score will represent worse global cognitive functioning; higher score will represent better global cognitive functioning. | From Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neuropsychiatric Symptoms | The measure used will be a checklist of symptoms involving the central nervous system. Minimum value: 0; Maximum value: 140. Lower score will represent better neuropsychiatric status; higher score will represent worse neuropsychiatric status. | From Baseline to Week 48 | 
| Change in Daily Living Functioning | Daily living functioning will be measured by a self-reported scale indicating daily living areas impaired. Minimum score: 0; Maximum score: 13. A lower score will represent better daily functioning; a higher score will represent worse daily functioning. | From Baseline to Week 48 | 
| Change in Depressive Symptoms | Depressive symptoms will be measured by a self-reported scale that will assess depressive symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better depressive status; a higher score will represent worse depressive status. | From baseline to week 48 | 
| Change in Anxiety Symptoms | Anxiety symptoms will be measured by a self-reported scale that will assess anxiety symptoms. Minimum score: 0; Maximum score: 21. A lower score will represent better anxiety status; a higher score will represent worse anxiety status. | From Baseline to Week 48 | 
| Change in Daily Perceived Stress | Perceived stress will be measured by a self-reported scale that will assess daily symptoms of perceived stress. Minimum score: 0; Maximum score: 40. A lower score will represent better perceived stress status; a higher score will represent worse perceived stress status. | From baseline to week 48 | 
| Change in Quality of Life | Quality of life will be measured by a self-reported scale that will assess global quality of life. Minimum score: 1; Maximum score: 4. A lower score will represent worse quality of life; a higher score will represent better quality of life. | From Baseline to Week 48 | 
| Change in Neuroimaging Markers | Neuroimaging markers will be assessed by 3T magnetic resonance imaging (MRI). The specific markers will be caudate nucleus, ventral striatum/nucleus accumbens, putamen, pallidum, thalamus, dorsomedial, dorsolateral, cingulate, ventromedial, medial orbitofrontal, and lateral orbitofrontal cortex. The outcome will be based on change in any of them. | From Baseline to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain, HIV-1 Infection