PROJECT SUMMARY/ABSTRACT
While combination antiretroviral therapy (cART) has significantly extended the lifespan of people with HIV
(PWH), nearly half of all PWH are estimated to have HIV-associated neurocognitive disorders (HAND). Even
mild forms of HAND, which are more prevalent in the cART era, significantly reduce quality of life for PWH and
can result in unemployment, lack of adherence to antiretroviral therapy, and increased mortality. With a rapidly
aging population, there is increased demand for improved understanding of the neural mechanisms of HAND –
especially prior to the onset of clinical symptoms – as older PWH are at an increased risk of developing HAND.
While dysfunction within the frontostriatal circuits has been implicated in HAND, the profile of disruption within
these circuits remains elusive. The goal of this work is to determine whether functional and structural
frontostriatal abnormalities present in older, virally suppressed PWH with minimal cognitive impairment.
Utilizing structural and functional MRI techniques, this proposal will address the following specific aims. My
dissertation research thus far (Aim 1) indicates that older, virally suppressed PWH with minimal cognitive
impairment have reduced frontostriatal functional connectivity compared to controls. In addition, increased HIV
disease severity and decreased neurocognitive function were associated with cortical thinning in PWH,
especially in the prefrontal cortex. In the next phase of my dissertation (F99, Aim 2), I will test the hypotheses
that frontostriatal white matter connections are compromised in older PWH compared to controls and that the
relationship between HIV disease severity and executive function is mediated by frontostriatal white matter
integrity. Results from these studies will provide critical insights into the neural mechanisms of HAND, inform
the development of early diagnostic methods, and help identify potential therapeutic targets. Upon completion
of my dissertation, I plan to complete a postdoctoral fellowship (K00, Aim 3) studying how comorbid conditions
(e.g. depression) in people with HIV contribute to HAND development and progression.