Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen
Condition: HIV Disease
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional

Summary: 
      In this study we 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. In a cohort of HIV-infected patients who are
      clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or
      Atripla, we propose to replace the EFV component with a new integrase inhibitor, elvitegravir
      (EVG) boosted with cobicistat (COBI), given as the EVG/COBI/FTC/TDF Single Tablet Regimen
      (STR) to evaluate the EFV-related neural alterations. This is a multidisciplinary study which
      involves a team of infectious disease experts in the field of HIV, neuroradiologists with
      expertise in fMRI and MRS techniques to study various central nervous system and psychiatric
      disorders and a psychiatrist with experience and expertise in research on abnormalities of
      affective and motivational processing in the context of neuropsychiatric disorders. We 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. We 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 STR 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
           STR, 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): Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)
Intervention type(s): Drug
Intervention description(s): Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks
Intervention MeSH terms: Tenofovir; Emtricitabine; Cobicistat; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir
Intervention model: Single Group Assignment
Intervention model description: Treatment switch study
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: HIV; neurocognitive symptoms; efavirenz; elvitegravir; neurometabolites