This is a prospective cohort study of 12 overweight (with one or more weight-related condition) or obese adults with well controlled HIV-1 on antiretroviral therapy (ART). An initial dose of tirzepatide (TZP) 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg. The investigators will collect the following information via review of the medical record: age, race/ethnicity, sex, medical conditions, medications, most recent standard of care HIV labs (including T-cell panel and HIV-1 viral load). The primary outcome will be the change in baseline body weight at 12 weeks. Secondary outcomes will be changes in body composition, liver fat content and liver stiffness, inflammatory markers, cardiometabolic markers (lipids and HbA1c), and monocytes at 12 weeks. There will be a 4-week safety follow up off TZP.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Tirzepatide is approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, obesity and overweight with at least one weight-related medical condition, and moderate to severe obstructive sleep apnea. An initial dose of TZP 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg.
John A Burns School of Medicine
Honolulu, Hawaii, United States
RECRUITINGChange in Baseline Body Weight
The primary outcome will be the change in baseline body weight (measured in lbs) at 12 weeks.
Time frame: 12 weeks
Change in Inflammatory Markers: GM-CSF
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: GM-CSF. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in cardiometabolic markers
We will evaluate HbA1c and a lipid profile at the baseline, week 12 and week 16 study visits.
Time frame: 12 weeks
Monocyte Subset Analysis
Monocyte subsets will be phenotyped from thawed/washed banked cryopreserved PBMCs (from blood drawn at baseline, week 12, and week 16) using a multiparametric panel of conjugated monoclonal antibodies: CD3, CD14, CD16, CD56, CD19, CD20, HLA-DR antibodies with Live/Dead fixable yellow dead cell stain (YARD). Data will be acquired on a 4-laser BD LSRFortessa Flow Cytometer with all compensation and gating analyses performed with the FlowJo analytical software to determine levels of classical (CD14 ++ CD16 -), intermediate (CD14 ++ CD16 +), non-classical (CD14 + CD16 ++), and transitional (CD14 + CD16 -) monocytes.
Time frame: Week 12 and week 16
Change in Inflammatory Markers: IFN-γ
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IFN-γ. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: IL-1β
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: IL-2
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-2. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: TNF-α
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: TNF-α. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: NFkB
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: NFkB. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Change in Inflammatory Markers: sCD163, and sCD14
All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: sCD163, and sCD14. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate.
Time frame: 12 weeks
Body composition
Body composition (total, peripheral and truncal fat, and lean tissue) by dual energy absorptiometry (DEXA)
Time frame: 12 weeks
Waist circumference
Changes in waist circumference over 12 weeks of therapy
Time frame: 12 weeks
Liver fat content
Changes in Liver fat content (Controlled Attenuation Parameter, CAP) over 12 weeks
Time frame: 12 weeks
Liver stiffness measurement (LSM)
Changes in Liver stiffness measurement (LSM) over 12 weeks
Time frame: 12 weeks
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