Advanced Neuroimaging Evaluation of CNS Changes Associated With Efavirenz Therapy Switch to an Raltegravir-based Regimen
Condition: HIV; HIV-associated Neurocognitive Disorder; Neurotoxicity
MeSH terms: Neurotoxicity Syndromes; Neurocognitive Disorders
Study type: Interventional

Summary: 
      In this study investigators will use a multi-modal imaging approach of MRS and fMRI to
      comprehensively assess the biological changes in the brain associated with EFV-based regimen
      (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local
      neurochemistry, and their correlation with neuropsychological function.
    

Detailed description: 
      In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of
      EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, investigators propose to replace the EFV
      component with an integrase inhibitor, Raltegravir (RAL), given as the RAL and FTC/TDF to
      evaluate the EFV-related neural alterations. This is a multidisciplinary study which will be
      lead by Dr. Nina Lin, in collaboration with the research teams of Dr. Alexander Lin, Director
      of the Center for Clinical Spectroscopy, and Dr. Emily Stern, Director of the Functional
      Neuroimaging Laboratory, both members of the Brigham and Women's Department of Radiology at
      Harvard Medical School, as well as Dr. Jane Epstein, a researcher in Dr. Stern's research
      group. Dr. Epstein is a staff psychiatrist at Brigham and Women's hospital with extensive
      experience and expertise in research on abnormalities of affective and motivational
      processing in the context of neuropsychiatric disorders. Investigators will utilize the
      established clinical research platform in the Infectious Disease outpatient clinical practice
      at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related
      studies and a large panel of HIV-infected patients motivated to be involved in clinically
      relevant research. Investigators propose to use advanced neuroimaging to measure biologically
      changes in the brain associated with long-term EFV use with the following specific aims:

        1. Determine changes in neurometabolites measured by MRS in the brain associated with
           long-term EFV use

        2. Assess for alterations in neural activity correlated with affective symptoms associated
           with EFV vs RAL use using fMRI, and their associations with changes in neurometabolites
           assessed by MRS, and with changes in cognition assessed by Trail Making and Digit
           Substitution Tests.

        3. Determine changes in emotion, cognition and sleep quality after switching from EFV to
           RAL, and how they correlate with subject treatment preference.

      This clinical study will extend our current understanding of EFV neurotoxicity by further
      defining the nature of these biological changes. Further elucidation of the neurobiological
      underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the
      quality of life and drug adherence of HIV-infected patients on ART, especially among older
      patients or those with baseline neuropsychiatric disorders, whom at baseline are more
      vulnerable to neurocognitive decline from long-term HIV infection.
    

Intervention name(s): Raltegravir
Intervention type(s): Drug
Intervention description(s): Switch from Atripla to Raltegravir 400mg BID + Truvada (FTC/TDF) for total of 8 weeks
Other intervention name(s): Raltegravir (Isentress) 400mg BID
Intervention MeSH terms: Raltegravir Potassium
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: HIV; HIV-associated neurocognitive disorder; neurotoxicity