The purpose of this randomized controlled trial is to understand how a cognitive-behavioral treatment (a form of psychological treatment) for depression changes the gut microbiome (micro-organisms that regulate the health of the gut), immune system, and the brain functioning in people living with HIV.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
150
CBT-AD is a behavioral intervention administered either in person or via Zoom. Each session lasts approximately 50 minutes. Participants will receive up to 12 individually delivered sessions over 4 months. Participants receive up to three individually delivered booster sessions through 6 months.
This treatment involves a single session integrating CBT for depression with CBT for adherence following our "Life-Steps" approach.
University of Miami Neuroimaging Facility
Coral Gables, Florida, United States
RECRUITINGCare Resource - Midtown Miami
Miami, Florida, United States
RECRUITINGChange in resting state activation of the negative valence system
Measured by functional Magnetic Resonance Imaging (fMRI)
Time frame: 6 Months
Change in connectivity of the negative valence system
Measured by functional Magnetic Resonance Imaging (fMRI)
Time frame: 6 Months
Depressive Symptoms
The Hamilton Rating Scale for Depression is an interviewer-administered measure that has a total score ranging from 0-52 with the higher score indicating greater depressive symptoms
Time frame: 6 Months
Alterations in gut microbiota
Measured via 16s sequencing of the gut microbiome using rectal swabs and fecal samples
Time frame: 4 months
Conserved transcriptional response to adversity (CTRA) leukocyte signaling pathway
Measured using Ribonucleic Acid (RNA) sequencing from peripheral blood mononuclear cells
Time frame: 4 Months
Soluble Markers of Microbial Translocation
Enzyme-linked immunosorbent assay (ELISA) methods will be employed to measure lipopolysaccharide binding protein (LBP) levels in plasma samples. Log10 will be the unit of measure.
Time frame: 4 Months
Soluble Markers of Immune Activation and Inflammation
Enzyme-linked immunosorbent assay (ELISA) methods will be employed to measure levels of monocyte activation markers (i.e., soluble CD14, soluble CD163) and pro-inflammatory cytokines (e.g., interleukin, high sensitivity c-reactive protein) in plasma samples. Log10 will be the unit of measure.
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Time frame: 4 Months
Soluble Markers of Dysregulated Neurotransmitter Synthesis
High performance liquid chromatography method with fluorescence will measure mean levels of the kynurenine/tryptophan and phenylalanine/tyrosine ratios in plasma samples. Log10 will be the unit of measure.
Time frame: 4 Months
Neurocognitive Functioning
Changes in mean levels of measures indexing executive functioning, attention, and affect regulation assessed in a comprehensive, interviewer-administered neuropsychological assessment battery. Units will be expressed as standardized scores (i.e., T scores).
Time frame: 6 Months