Cocaine Abstinence or Reduced Use May Retard Alterations in Brain Structure and Function, and Associated Cognitive Changes among African American Cocaine Users with HIV

ABSTRACT Despite the use of effective antiretroviral therapy (ART), HIV-related neurocognitive impairment (NCI) continues to be prevalent among people living with HIV. For more than 20-years, our investigation of HIV- associated comorbidities among African Americans (AAs) has demonstrated that while comorbidities are

prevalent among AAs living with HIV, other factors, such as cocaine use, may trigger or accelerate their impact. We have shown that although HIV increases the risk of coronary plaque, the detrimental effect of HIV/ART predominantly affects cocaine users rather than non-users. Likewise, our preliminary work showed

that while HIV was associated with NCI, the adverse effect of HIV primarily impacted cocaine users. Furthermore, our ongoing HEART study showed that a contingency management (CM) intervention is effective in achieving a sustained reduction in cocaine use among AA cocaine users with subclinical heart disease and

was associated with a concurrent decrease in coronary plaque burden. Cocaine use and NCI continue to disproportionately affect AAs, especially those living with HIV. As of now, there are no FDA-approved medications for cocaine addiction. We propose to investigate whether CM can be employed to decrease cocaine use and

slow cognitive decline among AA cocaine users. There is no single definitive biomarker that can measure cognitive decline; however, brain MRI may detect early structural changes in the brain that signify cognitive decline, prior to the onset of symptoms. Our latest brain MRI study revealed an independent association

between cocaine use and the length of its use with an increased severity of white matter hyperintensities (WMH) and a decrease in hippocampal (HP) volume among AAs. WMH are recognized as one of the most promising brain MRI markers of cognitive decline along with HP volume. Thus, we propose a 5-year study to

evaluate the effects of a 12-month CM intervention on the brain MRI biomarkers and cognitive performance assessed with NIH Toolbox Cognition Battery (NIHTB-CB) among AA cocaine users. We will recruit 180 AA cocaine users, ≥40-years of age, including an equal number of men and women with and without HIV, drawn

from our ongoing study (U01DA040325). Participants will undergo a 12-month CM to reinforce cocaine abstinence with an escalating cash incentive approach. In Aim 1, we will evaluate the effects of a 12-month CM on MRI measures of brain structure and function (WMH, HP volume, resting state fMRI and other measures)

and cognitive performance (NIHTB-CB). In Aim 2, we will evaluate the net effect of HIV on brain MRI measures and cognitive performance. In Aim 3, we will study whether changes in brain MRI measures during the 12- month CM period are associated with changes in cognitive performance. This study will establish the

effectiveness of a targeted intervention in reducing cocaine use and improving cognitive outcomes in AA cocaine users living with HIV, thereby addressing a recognized health disparity in the AA population.