IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment

HIV-1-infection Clinical Trial

Official title:

IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03416790
• Other study ID #: IMPAACT 2015
• Secondary ID: DAIDS ID 35123
• Status: Completed
• Start date: February 6, 2019
• Est. completion date: March 26, 2020

Study information

• Verified date: July 2020
• Source: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

IMPAACT 2015 is a cross-sectional, exploratory study that will investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. Findings from this study will advance understanding of the role of the CNS in HIV-1 persistence and its implications for future HIV-1 remission research.

Description:

IMPAACT 2015 is a cross-sectional, exploratory study aiming to investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. CSF will be examined for persistence of HIV-1 RNA or DNA despite antiretroviral therapy (ART) and for evidence of intrathecal inflammation. Perinatally-infected youth and young adults are of particular interest because there are very limited CSF data available in this population and reasons to be concerned about the CNS reservoir. In addition, measures of HIV-1 RNA in the CSF and associated biomarkers have not previously been explored in this population. A better understanding of viral persistence in the CSF, as well as CSF biomarker profiles, will provide preliminary data to move the field forward in understanding the role of the CNS in HIV-1 persistence and will have implications for future HIV-1 remission research.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 26, 2020
• Est. primary completion date: March 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 24 Years

Eligibility

Inclusion Criteria:

• 13-24 years of age (inclusive) at enrollment (i.e., on the day the participant is enrolled in the study)

• Spoken fluency in English or Spanish

• If not of legal age to provide independent informed consent: Parent or legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation

• If of legal age but not able to provide independent informed consent due to cognitive impairment as determined by site standard operating procedures (SOPs) and consistent with site institutional review board/ethics committee (IRB/EC) policies and procedures: Parent, legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation

• If of legal age and able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for study participation

• Has confirmed perinatal HIV-1 infection — with no documented evidence to suggest another route of transmission — based on review of available medical records

• Has been taking combination ART comprised of at least three agents from at least two classes of antiretroviral therapy for at least 12 consecutive months prior to enrollment as determined by the site investigator or designee based on participant or parent/guardian report and available medical records; regimen changes within the 12 months prior to enrollment are permitted, provided the virologic requirements in criterion below are met

• Has at least two consecutive documented plasma HIV-1 RNA values less than 40 copies/mL, at least three months apart, in the 12 months prior to enrollment; one of these values must be based on testing of a specimen collected within the 60 days prior to enrollment

• Has a Fluid Cognition Composite Score at least one-and-a-half standard deviations below the published normative mean (i.e., less than 78) based on administration of the NIH Toolbox Cognition Battery

Exclusion Criteria:

• Any ART interruption for more than seven consecutive days in the 12 months prior to enrollment

• Any HIV-1 RNA value greater than 200 copies/mL in the 12 months prior to enrollment

• Completed any of the NIH Toolbox subtests specified within 90 days prior to screening

• Any documented full scale intelligence quotient (IQ) score more than three standard deviations below the published normative mean (i.e., less than 55) or a Fluid Cognition Composite Score more than three standard deviations below the published normative mean (i.e., less than 55) based on administration of the NIH Toolbox Cognition Battery at screening

• Any documented diagnosis of autism spectrum disorder, schizophrenia, or other psychotic disorder

• Any known prior infection of the CNS that may be persistent or recurrent (e.g., cryptococcal meningitis, neurosyphilis)

• Any known non-HIV-related cause or significant contributing factor for cognitive impairment (e.g., birth injury, head injury, stroke, major or mild neurocognitive disorder due to a condition other than HIV) per Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-V) criteria

• Any known or suspected current contraindication to lumbar puncture

• Any current sensory or motor impairment severe enough to preclude participation in study evaluations (e.g., blindness, lack of upper limb control)

• If female and of reproductive potential (defined as having experienced menarche and having no documented history of a sterilization procedure), known or suspected pregnancy

• Any serious or otherwise clinically significant infection of the CNS or bloodstream (other than HIV-1 infection) within 30 days prior to enrollment

• Any live vaccine received within 30 days prior to enrollment

• Any other (non-live) vaccine received within 7 days prior to enrollment

• Received prolonged (more than 14 days) or high dose immunosuppressants within 30 days prior to enrollment (high dose would include >1 mg/kg prednisone (or equivalent) or any biologic immunosuppressant such as monoclonal antibody based therapy)

• Ever received any medication or other approved or investigational agent that may impact HIV-1 reservoirs, including but not limited to: HIV-1 vaccines, HIV-1 gene therapies, Anti-HIV-1 broadly neutralizing antibodies (e.g., VRC01), Anti-PD-1 or anti-PD-L1 antibody, Histone deacetylase inhibitors (e.g., vorinostat, romidepsin, panobinostat), Toll-like receptor agonists, Cytotoxic chemotherapies, Roxolitinib, and Sirolimus

Related Conditions & MeSH terms

• Cognitive Dysfunction
• HIV-1-infection

Locations

Country	Name	City	State
Puerto Rico	University of Puerto Rico Pediatric HIV/AIDS Research Program (CRS 6601)	San Juan
United States	Emory University School of Medicine (CRS 5030)	Atlanta	Georgia
United States	University of Colorado, Denver (CRS 5052)	Aurora	Colorado
United States	Johns Hopkins University (CRS 5092)	Baltimore	Maryland
United States	Boston Medical Center Pediatric HIV Program (CRS 5011)	Boston	Massachusetts
United States	Bronx-Lebanon Hospital Center (CRS 5114)	Bronx	New York
United States	Jacobi Medical Center (CRS 5013)	Bronx	New York
United States	David Geffen School of Medicine at University of California, Los Angeles (CRS 5112)	Los Angeles	California
United States	University of Southern California (CRS 5048)	Los Angeles	California
United States	St. Jude Children's Research Hospital (CRS 6501)	Memphis	Tennessee
United States	University of California, San Diego Mother-Child-Adolescent HIV Program (CRS 4601)	San Diego	California
United States	Seattle Children's Hospital (CRS 5017)	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
International Maternal Pediatric Adolescent AIDS Clinical Trials Group	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of quantifiable cell-free HIV-1 RNA CSF	Quantifiable cell-free HIV-1 RNA CSF defined as an HIV-1 RNA assay result of =20 copies/mL	Within 30 Days of Screening Initiation
Primary	Prevalence of detectable HIV-1 DNA in CSF cell pellets	Detectable HIV-1 DNA in CSF cell pellets defined as an HIV-1 DNA assay result of =1 copy in the cell pellet obtained from =10 ml of CSF	Within 30 Days of Screening Initiation
Secondary	Concentrations of inflammatory and neuronal injury biomarkers in CSF	Biomarkers to be evaluated include neopterin, neurofilament light chain (NFL), tyrosine (Y), lysine (K) and leucine (L) - 40kDa (YKL-40), interleukin (IL-6), C-reactive protein (CRP), interferon gamma-induced protein 10 (IP-10/CXCL10), monocyte chemoattractant protein 1 (MCP-1/CCL2), tumor necrosis factor (TNF-a), sCD14, soluble CD163 (sCD163), soluble intercellular adhesion molecule type 5 (sICAM-5) (immunoassays). Concentrations of each of these biomarkers in CSF will be summarized descriptively.	Within 30 Days of Screening Initiation
Secondary	Concentrations of inflammatory and neuronal injury biomarkers in plasma	Biomarkers to be evaluated include neopterin, neurofilament light chain (NFL), tyrosine (Y), lysine (K) and leucine (L) - 40kDa (YKL-40), interleukin (IL-6), C-reactive protein (CRP), interferon gamma-induced protein 10 (IP-10/CXCL10), monocyte chemoattractant protein 1 (MCP-1/CCL2), tumor necrosis factor (TNF-a), sCD14, soluble CD163 (sCD163), soluble intercellular adhesion molecule type 5 (sICAM-5) (immunoassays). Concentrations of each of these biomarkers in plasma will be summarized descriptively.	Within 30 Days of Screening Initiation
Secondary	Associations of the above-listed secondary outcomes with the primary outcomes	Associations will be assessed with Spearman correlations (and corresponding confidence intervals).	Within 30 Days of Screening Initiation