MARCH Central Nervous System Substudy

• 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 [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  using CogState testing at 5 timepoints, weeks 0, 12, 24, 48, 96
• 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 [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

  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

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

participants in the MARCH main study who are eligible for the CNS substudy and provide written informed consent for participation

• Drug: Arm 1 TNucleotide Analogue Reverse Transcriptase Inhibitors and Boosted Protease Inhibitors
  NRTI+PI
  Other Names:

  • tenofovir
  • emtricitabine
  • zidovudine
  • lamivudine
  • abacavir
  • Ritonavir
  • lopinavir
  • darunavir
  • atazanavir
  • fosamprenavir
• Drug: Arm 2 Maraviroc and Protease Inhibitors
  maraviroc + PI
  Other Names:

  • maraviroc
  • Ritonavir
  • lopinavir
  • darunavir
  • atazanavir
  • fosamprenavir
• Drug: Arm 3 Maraviroc and Nucleotide Analogue Reverse Transcriptase Inhibitors
  maraviroc + NRTI
  Other Names:

  • maraviroc
  • tenofovir
  • emtricitabine
  • zidovudine
  • lamivudine
  • abacavir

• NRTI + PI
  This is the randomisation of the main study, Arm 1
  Intervention: Drug: Arm 1 TNucleotide Analogue Reverse Transcriptase Inhibitors and Boosted Protease Inhibitors
• maraviroc + PI
  this is the randomisation of the main study, Arm 2
  Intervention: Drug: Arm 2 Maraviroc and Protease Inhibitors
• maraviroc + NRTI
  this is the randomisation of the main study, Arm 3
  Intervention: Drug: Arm 3 Maraviroc and Nucleotide Analogue Reverse Transcriptase Inhibitors

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