Assessment of the HIV CNS Reservoir, Neurological and Neuro-cognitive Effects, and Source of Rebound HIV in CNS

NCT02470351 | Completed

• 1 other identifier: SEARCH 026
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to describe in depth the CNS, CNS HIV reservoir and CNS viral rebound in consenting SEARCH 019 subjects prior to, during and after the SEARCH 019 study intervention (VHM + ART or ART only), at 1) baseline, 2) end of study intervention and start of ART interruption, 3) viral rebound (if occurring) or mid-way during observed ART interruption, and 4) at the end of ART interruption. Study SEARCH 026 itself does not employ any therapeutic interventions. However, consenting subjects will participate in lumbar puncture, non-contrast MRI + MRS, and neuropsychological testing at at least three and at most four time points. Any of the 15 subjects to be enrolled in SEARCH 019 may consent to study SEARCH 026 participation and hence a maximum of 15 subjects may enroll. As this is a sub-study, data will be shared from study SEARCH 019 and no interventions (venipunctures) will be repeated unnecessarily.

Conditions

Acute HIV Infection; HIV CNS Involvement

Outcome Measures

Primary Outcomes (2)

• CSF vs. plasma HIV viral load in VHM+ART and ART alone

  Difference between CSF vs. plasma HIV viral load in VHM+ART and ART alone groups at study baseline (prior to VHM initiation), at time just before ATI, midway through ATI period (if not preceded by viral rebound) and at viral rebound or end of ATI observation period. Unit of measure: copies/mL.

  34 weeks

• Establishment of HIV in the CNS and the source of resurgent CSF HIV RNA between plasma and CSF variants prior to ART and after VHM intervention.

  34 weeks

Secondary Outcomes (8)

• Change in levels over time of CSF neopterin (nmol/L), sCD14 (ng/mL), CSF MCP-1 (pg/dL), IP-10 (nmol/L), sCD163 (ng/mL), IL-6 (pg/mL), and HIV RNA (copies/mL) value by single copy assay

  34 weeks

• Change over time in appearance of structural and T2 MRI scans including evidence of neuroinflammatory lesions

  34 weeks

• Change over time in concentrations of creatine (Cr) of choline (Cho), myoinositol (mI), and n-acetylaspartate (NAA) in the basal ganglia, occipital grey matter, and frontal white matter. Unit of measure of all metabolites is mM.

  34 weeks

• Measurement ratios with respect to creatinine (Cr) of choline (Cho), myoinositol (mI), and n-acetylasparate (NAA) in the basal ganglia, occipital grey matter, and frontal white matter. Unit of measure for all metabolites is mM.

  34 weeks

• Change over time in measures of fractional anisotropy on diffusion tensor imaging (DTI) in whole brain and voxel-based analysis

  34 weeks

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Any of the 15 subjects to be enrolled in SEARCH 019 may consent to study SEARCH 026 participation and hence a maximum of 15 subjects may enroll.

You may not qualify if:

• Subject is pregnant or breast-feeding.
• Any contraindication to lumbar puncture, such as history of bleeding diathesis or known cerebral mass lesion
• Any contraindication to MRI or MRS such as an implanted pacemaker, some older intracranial aneurysm clips, cochlear implants, certain prosthetic devices, implanted drug infusion pumps, neurostimulators, bone-growth stimulators, certain intrauterine contraceptive devices, or any other type of iron-based metal implants. MRI is also contraindicated in the presence of some internal metallic objects such as bullets or shrapnel, as well as most surgical clips, pins, plates, screws, metal sutures, or wire mesh.
• Subject has been diagnosed with a serious medical or psychiatric illness that, in the opinion of the site investigator, would interfere with his or her ability to adhere to study requirements or to give informed consent.
• Subject has active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with his or her ability to adhere to study requirements or to give informed consent.

Sponsors & Collaborators

• SEARCH Research Foundation: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

SEARCH Thailand

Bangkok, Bangkok, 10330, Thailand

Location

Biospecimen

Retention: SAMPLES WITH DNA

HIV RNA standard quantitation will be completed using the Roche COBAS/Amplicor HIV-1 Viral Load v2.0 assay, with a lower limit of quantitation of 20cps/mL. Single Copy Assay (SCA) HIV RNA quantitation in the setting of ART will be performed using 5-10 ml of CSF. In addition, cell associated HIV-DNA (total, integrated and 2LTR circles in total CD4+ T cells will be assessed at CRC-CHUM.

Study Officials

• Nittaya - Phanuphak, MD, PhD

  SEARCH Research Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nittaya Phanuphak, MD, PhD

Study Record Dates

• First Submitted: June 2, 2015
• First Posted: June 12, 2015
• Study Start: January 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: March 1, 2016
• Last Updated: April 26, 2016

Record last verified: 2016-03

Locations

TH (1)