Cognitive Impairment, HIV-1 Infection
Conditions
Keywords
Brain, HIV-1 Infection
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.
Interventions
None listed
Sponsors
Institut de Diagnostic per la Imatge
Institut d'Investigació Biomèdica de Bellvitge
Consorci Sanitari de Terrassa
BCN Checkpoint
Germans Trias i Pujol Hospital
IrsiCaixa
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early Treated Patients 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. | 12 |
| Regularly Treated Patients 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. | 15 |
| Seronegative Volunteers HIV-uninfected volunteers, matched to age, sex, and educational level with groups A and B. | 15 |
| Total | 42 |
Baseline characteristics
| Characteristic | Early Treated Patients | Seronegative Volunteers | Regularly Treated Patients | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 15 Participants | 15 Participants | 42 Participants |
| Age, Continuous | 34 years STANDARD_DEVIATION 10 | 32 years STANDARD_DEVIATION 10 | 31 years STANDARD_DEVIATION 9 | 32 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 15 Participants | 15 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Spain | 12 Participants | 15 Participants | 15 Participants | 42 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 15 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 12 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 12 | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: From Baseline to Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Global Cognitive Functioning | 0.08 score on a scale | Standard Deviation 0.26 |
| Regularly Treated Patients | Change in Global Cognitive Functioning | 0.31 score on a scale | Standard Deviation 0.28 |
| Seronegative Volunteers | Change in Global Cognitive Functioning | 0.25 score on a scale | Standard Deviation 0.19 |
Secondary
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.
Time frame: From Baseline to Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Anxiety Symptoms | -5.18 score on a scale | Standard Deviation 3.46 |
| Regularly Treated Patients | Change in Anxiety Symptoms | -2.00 score on a scale | Standard Deviation 2.93 |
| Seronegative Volunteers | Change in Anxiety Symptoms | -1.30 score on a scale | Standard Deviation 2.49 |
Secondary
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.
Time frame: From Baseline to Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Daily Living Functioning | 0.54 score on a scale | Standard Deviation 1.69 |
| Regularly Treated Patients | Change in Daily Living Functioning | 0.33 score on a scale | Standard Deviation 2.01 |
| Seronegative Volunteers | Change in Daily Living Functioning | 0.30 score on a scale | Standard Deviation 0.82 |
Secondary
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.
Time frame: From baseline to week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Daily Perceived Stress | -7.55 score on a scale | Standard Deviation 3.88 |
| Regularly Treated Patients | Change in Daily Perceived Stress | -6.50 score on a scale | Standard Deviation 9.24 |
| Seronegative Volunteers | Change in Daily Perceived Stress | 1.40 score on a scale | Standard Deviation 4.72 |
Secondary
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.
Time frame: From baseline to week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Depressive Symptoms | -3.55 score on a scale | Standard Deviation 2.58 |
| Regularly Treated Patients | Change in Depressive Symptoms | -0.50 score on a scale | Standard Deviation 3.84 |
| Seronegative Volunteers | Change in Depressive Symptoms | -0.60 score on a scale | Standard Deviation 1.43 |
Secondary
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.
Time frame: From Baseline to Week 48
Secondary
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.
Time frame: From Baseline to Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Neuropsychiatric Symptoms | -2.90 score on a scale | Standard Deviation 8.76 |
| Regularly Treated Patients | Change in Neuropsychiatric Symptoms | 0.33 score on a scale | Standard Deviation 7.58 |
| Seronegative Volunteers | Change in Neuropsychiatric Symptoms | 0.30 score on a scale | Standard Deviation 5.77 |
Secondary
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.
Time frame: From Baseline to Week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Treated Patients | Change in Quality of Life | 0.18 score on a scale | Standard Deviation 0.4 |
| Regularly Treated Patients | Change in Quality of Life | 0.08 score on a scale | Standard Deviation 0.51 |
| Seronegative Volunteers | Change in Quality of Life | 0.10 score on a scale | Standard Deviation 0.73 |