MARCH Central Nervous System Substudy

Kirby Institute28 enrolled

Overview

This substudy is a prospective, observational, open-label, randomised study within the MARCH study. The purpose of this substudy is to investigate the changes in cerebral function parameters at 5 timepoints over 96 weeks of the three different treatment arms within the MARCH study. The investigators hypothesise that there will be improvements in cerebral function in those patients randomised, as part of the parent study, into the maraviroc arms. the assessments in this CNS substudy will include: 1. Neurocognitive function as assessed by a computerised testing battery called CogState; 2. changes in cerebral metabolites as measured via 1H Magnetic Resonance Spectroscopy (1H-MRS) In those randomised to the maraviroc arms (arms 2 and 3) there is an optional Lumbar puncture at week 48. The cerebrospinal fluid will be used to measure maraviroc levels and an ultrasensitive CSF HIV-1 viral load. These results will be matched with levels in the plasma.

this is detailed above, this is a substudy of MARCH

Study Type

OBSERVATIONAL

Enrollment

Conditions

HIV-1 Infection

Interventions

Arm 1 TNucleotide Analogue Reverse Transcriptase Inhibitors and Boosted Protease Inhibitors

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Provision of written, informed consent for participation in the substudy * Enrolled into the substudy either at or before the week 0 visit of the main study Exclusion Criteria: * Pre-existing CNS diseases * Recent head injury (past three months) * Current history of major depression or psychosis

Locations (6)

Fundación IDEAA

Buenos Aires, Buenos Aires, Argentina

Hospital Ramos Mejía

Buenos Aires, Argentina

CAICI

Rosario, Argentina

Chulalongkorn University Hospital

Bangkok, Bangkok, Thailand

Brighton & Sussex University NHS Trust

Brighton, Sussex, United Kingdom

Imperial Healthcare, St. Mary's Hospital

London, United Kingdom

Outcomes

Primary Outcomes

To assess changes in NC function over 96 weeks, measured via a computerised testing battery in HIV-infected subjects stable on antiretroviral therapy randomised to three different treatment approaches

using CogState testing at 5 timepoints, weeks 0, 12, 24, 48, 96

Time frame: 96 weeks

To assess changes in cerebral metabolites over 96 weeks, measured via 1H Magnetic Resonance Spectroscopy (1H-MRS), in HIV-infected subjects stable on antiretroviral therapy randomised to three different treatment approaches

Assessment of CNS metabolites via 1H-MRS at week 0, 48, 96 * Cerebral metabolites in frontal white and grey voxels, and basal ganglia will be measured * Measurable metabolites will include assessment of neuronal markers, N-acetyl-aspartate, and inflammatory markers, myo-Inositols and Choline

Time frame: 96 weeks

Secondary Outcomes

to assess CSF HIV-1 RNA and CSF maraviroc concentration (in the MVC treatment arms) versus plasma HIV -1 RNA and MVC concentration after 48 weeks of therapy

A LP examination at week 48 (optional and only in the MVC treatment arms, and only if there is no contraindication to LP) to assess, with matched plasma samples: * CSF MVC concentration * CSF HIV-1 RNA * CSF biomarkers

Time frame: 48 weeks