The goal of the Treatment Research Investigating Depression Effects on Neuroimmune Targets – also known as TRIDENT – study is to examine how decreasing depression alters MGB axis pathways in people living with HIV (PLWH). To lower depression among PLWH, Cognitive-Behavioral Therapy for Adherence and Depression Treatment (CBT-AD), which is an evidence-based treatment for poor HIV/AIDS antiretroviral therapy adherence and depression, will be administered.

Adam Carrico, Ph.D.

“We have assembled a strong team with expertise in the microbiome, gene expression, and neuroHIV to understand how CBT-AD related reductions in depression could influence different aspects of the MGB axis in PLWH,” said Dr. Adam Carrico, Ph.D., professor of public health sciences and psychology, who will serve as principal investigator.  Dr. Carrico is also the Director of the Prevention Science and Community Health Division in the Miller’s School’s Department of Public Health Sciences.

People living with HIV experience damage to the gastrointestinal tract during acute HIV infection. The alterations that occur in the gut result in immune dysregulation through a process called dysbiosis and translocation of inflammatory microbial products into the periphery. This dysregulation of the immune system is known to heighten the risk for depression and other neuropsychiatric disorders in PLWH.

Approximately 150 participants will be enrolled in the randomized controlled trial. The study seeks to understand the underlying mechanisms that are taking place during HIV infection between the microbiome, gastrointestinal tract, immune system, and brain functioning using fMRI. Clinical research is needed to advance scientific knowledge on the interactions of the MGB axis to advance depression treatment for PLWH.

The study will involve participants that will receive the CBT-AD treatment as well as a wait-list control (WLC) group. CBT-AD participants will receive up to 12 individual sessions of treatment over 4 months. WLC participants will provide important comparative results and will also have the opportunity to receive CBT-AD after six months. All participants will complete a final follow-up assessment following 10 months implementation of the trial.

Periodic assessments will be made to evaluate the effects of the treatment, including changes in the microbiome, soluble immune markers relevant to HIV immunology, and leukocyte signaling to measure the conserved transcriptional response to adversity (CTRA).

In addition to Dr. Carrico, principal investigators include Steven Safren, Ph.D., professor at the University of Miami Department of Psychology and Director of the UM Center for HIV and Research in Mental Health; and Robert Paul, Ph.D., professor of behavioral medicine at the University of Missouri – St. Louis and Director of the Missouri Institute of Mental Health.

Steven Safren, Ph.D.

“I am excited to have been invited to join this stellar team and be able to use our evidence-based depression treatment [CBT-AD] to learn how improved depression will affect the MGB axis,” Dr. Safren said.

“This study will break new ground by leveraging a unique clinical trial design and novel analytic strategies to delineate the complex interplay between peripheral and central mechanisms that underlie mood disorders among PLWH.  Findings from this study will have direct clinical relevance and high potential to improve life quality and overall health among PLWH,” Dr. Paul said.

Robert Paul, Ph.D.

The primary outcomes of task-based activation and resting state connectivity of the negative valence system will be derived from fMRI scans that will be conducted on the Coral Gables campus by co-investigator Roger McIntosh, Ph.D., associate professor at the University of Miami Department of Psychology.

Roger McIntosh, Ph.D.

“Understanding temporal dynamics of the mind-body connection and the extent to which CBT-AD contributes to functional brain changes under different conditions, e.g., resting, interoception, and emotional regulation, may be important for the overall disease management in PLWH,” Dr. McIntosh said.

TRIDENT will generate multi-level, high dimensional data on the MGB axis among people with co-occurring HIV and depression. Findings from the data will guide the development of new pharmacologic and behavioral treatments for depression and its neurobehavioral substrates in PLWH.

Written by Veronica Bustabad

Published on October 26, 2021