Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen

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.