Treatment Research Investigating Depression Effects on Neuroimmune Targets (TRIDENT)

The overarching goal of this randomized controlled trial (RCT) is to identify the causal pathways that drive depressive symptoms among people with HIV (PWH). The scientific premise is that evidence-based depression treatment is an innovative, experimental probe to determine the neural substrates of depression and mechanistic relevance of microbiome-gut-brain (MGB) axis changes during and after Cognitive-Behavioral Therapy for Adherence and Depression (CBT-AD) on brain and behavioral function. The proposed causal pathway is that reductions in depressive symptoms following the delivery of CBT-AD treatment will trigger a cascade of alterations in the MGB axis. Specifically, CBT-AD related decreases in depressive symptoms will induce alterations in gut dysbiosis, decrease microbial translocation, and improve soluble neuroactive markers of peripheral immune dysregulation. Our efforts to elucidate the immunologic mechanisms whereby CBT-AD could improve neurobehavioral outcomes will also focus on an established leukocyte signaling pathway, the Conserved Transcriptional Response to Adversity (CTRA), which has been shown to be responsive to behavioral interventions and psychosocial factors outside of HIV.

Inclusion criteria

• Age 18 or older
• Speaks and reads English
• Verified HIV+ status with antiretroviral medications bearing his/her name
• Current diagnosis on Major Depressive Disorder (MDD) using a structured clinical interview (DIAMOND) or Hamilton Rating Scale for Depression scores of 7 or greater
• If prescribed antidepressants, on a stable regimen and dose for at least 2 months
• Suppressed HIV viral load (< 200 copies/mL)
• Able to complete Functional Magnetic Resonance Imaging (fMRI) scans (i.e., no claustrophobia, no metal implants, no pacemaker, and BMI < 40)

Exclusion criteria

• Unable to provide informed consent
• Active, untreated major mental illness
• Pregnancy at baseline
• Received CBT for depression in the past 2 years
• 5. Otherwise eligible but does not complete the run-in period that includes the baseline assessment, biospecimen collection, the fMRI visit, and a separately scheduled randomization visit