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

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.

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