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

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. 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.