Neuroinflammation and Neurodegeneration in HIV-positive Subjects Switched and Initially Treated With INSTI

NCT04887675 | Unknown

• 1 other identifier: UNoviSad
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Since the HIV changed its course to the chronic disease, high incidence of metabolic syndrome both in HIV positive and negative subjects has become an issue. Given the successful peripheral suppression of HIV after introduction of combined antiretroviral therapy (cART), comorbidities associated with aging and cognitive functioning, play the main role in the overall quality of life and adherence to the therapy. Continuous low-level neuroinflammation results in continuous and diffuse neuronal death or dysfunction leading to a certain level of neurodegeneration. Additionally, metabolic syndrome contributes to neurodegeneration causing damage to the brain vasculature and provoking the ischemic incidents. The aim of this study would be to explore the influence of switching to the INSTI based cART using neuroimaging biomarkers of inflammation and neurodegeneration. The second aim would be to monitor these neuroimaging biomarkers in patients receiving INSTI-based cART in a one-year follow-up period. Additionally, we would compare the markers of metabolic syndrome and cognitive functioning (executive functions) in HIV-positive patients after switching to INSTI-based cART and in HIV-positive patients receiving INSTI-based cART from the start. This study represents a single-center, prospective, interventional, two-armed single study. Arm I will include 60 patients on PI/EFV based ART, stable on treatment, who are switched to INSTI based regimen at the beginning of the study due to side effects or long-term toxicities like hyperlipidemia, diarrhea, (PI), insomnia, headache (EFV), high Framingham score (PI/EFV). Arm II will include 60 patients initially on INSTI-based ART, stable on treatment. The same data sets will be collected for both groups of patients. The variables collected will be related to metabolic syndrome (levels of LDL and HDL cholesterol, triglycerides, fasting insulin, glucose, blood pressure, waist circumference, waist to hip and waist to height ratio), performance on neurocognitive tests and MR spectroscopy neuroinflammation and neurodegeneration markers at the beginning of the study, as well as in 12 months follow up. Presence of steatosis and visceral fat thickness will be assessed using ultrasonography of abdomen. The primary imaging will be performed at the time of enrollment of patients, along with the neurocognitive testing and blood sampling. The secondary imaging (follow up) will be performed 12 months after the initial, also followed by neurocognitive assessment and blood sampling. Anthropometric measurements will be acquired at the time of blood sampling. Statistical analysis will be performed after collecting the data. Our work could significantly contribute to the better life quality in the aging of HIV positive subjects in the domain of cognitive functioning, tightly associated with adherence and overall life quality.

Conditions

HIV I Infection; HIV Associated Lipodystrophy; Metabolic Syndrome; Aging

Outcome Measures

Primary Outcomes (1)

• Levels od inflammatory biomarkers in patients switched to INSTI based regimens

  We will assess neuroimaging biomarkers obtained on magnetic resonance spectroscopy. These markers are: N-acetyl aspartate (NAA, marker of neuronal density and function), choline (Cho, marker of membrane metabolism and degradation), myoinositol (mI, marker of glial proliferation) and creatine (Cr, reference marker and marker of energy depot). These markers will be derived as ratios: NAA/Cr, Cho/Cr and mI/Cr.

  1 year

Secondary Outcomes (2)

• Performance performance on neurocognitive test in patients initially treated with INSTI based regimens

  1 year

• Incidence of metabolic syndrome in patients initially treated with INSTI based regimens

  1 year

Study Arms (2)

Patients switched from PI/EFV based ART to INSTI based ART

ACTIVE COMPARATOR

60 patients on PI/EFV based ART, stable on treatment (undetectable viral load for at least 6 months). At the beginning of the study they are switched to INSTI based regimen. The reasons for the switch will be side effects or long-term toxicities like hyperlipidemia, diarrhea, (PI), insomnia, headache (EFV), high Framingham score (PI/EFV)

Diagnostic Test: MRI

Patients initially treated with INSTI based regimens

ACTIVE COMPARATOR

60 patients initially started on INSTI based ART (raltegravir and dolutegravir), stable on treatment (undetectable viral load for at least 6 months).

Diagnostic Test: MRI

Interventions

MRI DIAGNOSTIC_TEST

Both groups with undergo neuroimaging on 3T magnetic resonance unit (Trio Tim, Siemens, Erlangen, Germany) in the Center for Diagnostic Imaging, Oncology Institute of Vojvodina, Serbia. Multivoxel MRS will be performed in the supratentorial cerebral parenchyma, covering white matter of frontal and parietal lobes, as well as cortical grey matter in frontal and parietal lobes and the whole cingulate gyrus.

Patients initially treated with INSTI based regimens; Patients switched from PI/EFV based ART to INSTI based ART

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male (in order to eliminate the hormonal influences on the levels of brain metabolites),
• older than 18 years,
• HIV seropositivity confirmed on PCR testing,
• undetectable viral load for over one year,
• conventional magnetic resonance imaging (MRI) normal.
• In group I, the additional criterion would be stable cART not containing INSTI for over one year.

You may not qualify if:

• active infiltrative or infective/opportunistic neurological illness,
• chronic neurological diseases (multiple sclerosis, vascular and non-vascular dementia, other neurodegenerative conditions),
• active abuse of narcotic drugs,
• hepatitis B or C coinfection,
• deep white matter lesions (focal or diffuse, such as lacunar stroke, leukoaraiosis, infiltrative or infective foci, metastases etc.),
• International HIV Dementia Scale (IHDS) score \<10 (only neuro-asymptomatic subjects would be included in the study), and
• contraindications for MRI examination

Sponsors & Collaborators

• University of Novi Sad: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Faculty of Medicine, University of Novi Sad

Novi Sad, 21000, Serbia

RECRUITING

MeSH Terms

Conditions

HIV-Associated Lipodystrophy Syndrome; Metabolic Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders

Study Officials

• Snezana Brkic

  University of Novi Sad

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Snezana Brkic

CONTACT

+38163570350; brkicsnezana@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor, Dean of Faculty of Medicine

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 14, 2021
• Study Start: May 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: October 1, 2022
• Last Updated: December 1, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)