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

Completed

• Conditions: Cognitive Impairment; HIV-1 Infection

• Registration Number: NCT03835546
• Lead Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-10-26
• Primary Completion: 2016-12-23
• Study Completion: 2018-06-29
• Study First Submitted: 2018-09-25
• Study First Submitted QC: 2019-02-07
• Study First Posted: 2019-02-08
• Results First Submitted: 2020-04-10
• Results First Submitted QC: 2020-05-15
• Results First Posted: 2020-06-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-22
• Last Update Posted: 2023-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Global Cognitive Functioning	From Baseline to Week 48	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.

Secondary Outcome Measures

Name	Time	Method
Change in Neuroimaging Markers	From Baseline to Week 48	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.
Change in Depressive Symptoms	From baseline to week 48	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.
Change in Anxiety Symptoms	From Baseline to Week 48	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.
Change in Neuropsychiatric Symptoms	From Baseline to Week 48	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.
Change in Daily Living Functioning	From Baseline to Week 48	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.
Change in Daily Perceived Stress	From baseline to week 48	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.
Change in Quality of Life	From Baseline to Week 48	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.