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

NCT03416790 | Completed DMC

• 2 other identifiers: IMPAACT 2015DAIDS ID 35123
• Study Type: observational
• Target: 24
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

HIV-1-infection

Keywords

Central Nervous System; HIV Persistence; HIV Reservoirs

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Concentrations of inflammatory and neuronal injury biomarkers in CSF

  Within 30 Days of Screening Initiation

• Concentrations of inflammatory and neuronal injury biomarkers in plasma

  Within 30 Days of Screening Initiation

• Associations of the above-listed secondary outcomes with the primary outcomes

  Within 30 Days of Screening Initiation

Eligibility Criteria

• Age: 13 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Perinatally HIV-1-infected youth and young adults (13-24 years of age) with cognitive impairment, on suppressive antiretroviral therapy, from study sites in the United States

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (12)

University of Southern California (CRS 5048)

Los Angeles, California, 90089, United States

Location

David Geffen School of Medicine at University of California, Los Angeles (CRS 5112)

Los Angeles, California, 90095, United States

Location

University of California, San Diego Mother-Child-Adolescent HIV Program (CRS 4601)

San Diego, California, 92103, United States

Location

University of Colorado, Denver (CRS 5052)

Aurora, Colorado, 80045, United States

Location

Emory University School of Medicine (CRS 5030)

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University (CRS 5092)

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center Pediatric HIV Program (CRS 5011)

Boston, Massachusetts, 02118, United States

Location

Bronx-Lebanon Hospital Center (CRS 5114)

The Bronx, New York, 10457, United States

Location

Jacobi Medical Center (CRS 5013)

The Bronx, New York, 10461, United States

Location

St. Jude Children's Research Hospital (CRS 6501)

Memphis, Tennessee, 38105, United States

Location

Seattle Children's Hospital (CRS 5017)

Seattle, Washington, 98105, United States

Location

University of Puerto Rico Pediatric HIV/AIDS Research Program (CRS 6601)

San Juan, 00936, Puerto Rico

Location

Biospecimen

Retention: SAMPLES WITH DNA

CSF, PBMC, plasma

Study Officials

• Ann Chahroudi, MD, PhD

  Emory University

  STUDY CHAIR

• Thor Wagner, MD

  University of Washington

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 31, 2018
• Study Start: February 6, 2019
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: July 8, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); PR (1)