Tirzepatide's Effects on Epigenetic Aging and Metabolic Restoration in Virally Suppressed People With HIV

Reversing the Biological Clock: Tirzepatide's Effects on Epigenetic Aging and Metabolic Restoration in Virally Suppressed People With HIV

This study is a pilot, open-lable, two-arm study. The investigators will enroll virally suppressed people living with HIV and obesity to evaluate the effect of tirzepatide on epigenetic aging, assessed by DNA methylation-based clocks using peripheral blood. In parallel, imaging studies will be performed to assess changes in body composition and intrahepatic fat content.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus; Metabolic Syndrome; Human Immunodeficiency Virus (HIV); Dyslipidaemia; Obesity & Overweight; Metabolic Dysfunction Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Adult people living with HIV, who are virally suppressed, defined as plasma HIV viral load is < 200 copies/mL within 6 months before enrollment. Participants have to have BMI > 30 kg/m2.

Exclusion Criteria:

• Participants cannot have undergone treatment with any incretin-based treatment within the past 90 days before enrollment. Participants cannot have any AIDS-defining illnesses, active malignancy, or history of decompensated liver failure. Participants cannot be pregnant. Participants cannot have history of acute pancreatitis or a family history of medullary thyroid cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; Participants enrolled in the interventional arm will undergo baseline imaging and blood testing, followed by an 8-week diet and nutrition consultation delivered via a smartphone-based application. Participants will then receive tirzepatide treatment for 25 weeks, after which imaging and blood testing will be repeated. Tirzepatide will subsequently be withheld for 24 weeks, with imaging and blood testing repeated once more to assess the persistence of treatment effect. Bictegravir PK/PD study will be done to assess whether tirzepatide will affect bictegravir pharmacokinetics during the study.	Drug: Tirzepatide; Tirzepatide will be given to the study arm after 8 weeks of diet and nutrition services. Study arm will receive a total of 25 weeks of tirzepatide.
No Intervention: Standard of care; Participants enrolled in the standard of care arm will undergo identical imaging and blood testing, but without bictegravir PK/PD. They will receive diet and nutrition consult delivered via a smartphone-based application throughout the study course.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Second generation epigenetic aging clock	PCGrimAge will be used to study the measured epigetic age and differences with chronological age in years.	Baseline, week 33, week 57
Third generation epigenetic aging clock	DunedinPACE will be used to assess the pace of aging, quantifying years of physiological decline per chronological year.	Baseline, week 33, week 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic triglycerides	Intrahepatic triglycerides will be measured using Magnetic Resonance Imaging Proton Density Fat Fraction (MRI PDFF).	Baseline, week 33, week 57
Change in body composition assessed by dual-energy X-ray absorptiometry (DXA)	Lean body mass and fat mass will be measured in kilograms.	Baseline, week 33, week 57
Change from baseline in body fat mass measured by bioelectrical impedance analysis (BIA)	Bioelectrical impedance analysis will be used to assess fat mass in kilograms.	Baseline, week 33, week 57
Patient reported outcome	Patient reported outcome will be assessed using HIV symptom index	Baseline, week 33, week 57
Drinking habits	Alcohol Use Disorders Identification Test (AUDIT) will be used to assess drinking habits for all participants.	Baseline, week 33, week 57
Body weight	Body weight will be measured in kilograms.	Baseline, week 8, week 13, week 21, week 33, week 57
Waist circumference	Waist circumference will be measured in centimeters	Baseline, week 8, week 13, week 21, week 33, week 57
Inflammation markers	C-reactive protein will be measured in mg/dL.	Baseline, week 33, week 57
Total bilirubin	Total bilirubin will be measured in mg/dL.	Baseline, week 33, week 57
Alanine transaminase	ALT will be measured in U/L.	Baseline, week 33, week 57
Aspartate transminase	AST will be measured in U/L.	Baseline, week 33, week 57
Fibrosis-4 index	Fibrosis-4 index is calculated using AST, ALT, platelet and age.	Baseline, week 33, week 57
A1c	HbA1c will be measured in percentage.	Baseline, week 33, week 57
Fasting plasma glucose	Fasting plasma glucose will be measured in mg/dL.	Baseline, week 33, week 57
Fasting serum insulin	Insulin will be measured in µIU/mL.	Baseline, week 33, week 57
Change from baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	HOMA-IR will be calculated using fasting insulin and glucose.	Baseline, week 33, week 57
Lipid profile	Lipid profile includes total cholesterol, HDL, LDL, TG measured in mg/dL.	Baseline, week 33, week 57
Creatinine	Creatinine will be measured in mg/dL.	Baseline, week 33, week 57
NT-proBNP	NT-proBNP will be measured in pg/L.	Baseline, week 33, week 57
Blood pressure	Blood pressure will be measured in millimeter mercury. Both systolic blood pressure and diastolic blood pressure will be measured.	Baseline, week 8, week 13, week 21, week 33, week 57

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bictegravir pharmacokinetics (PK)	Bictegravir PK is assessed via serial blood sampling at 7 timepoints over 24 hours, with AUC constructed after calibrating serial drug levels.	Baseline, between week 16-32
Tenofovir pharmacokinetics (PK)	Tenofovir PK is assessed via serial blood sampling at 7 timepoints over 24 hours, with AUC constructed after calibrating serial drug levels	Baseline, between week 16-32.
Emtricitabine pharmacokinetics (PK)	Emtricitabine PK is assessed via serial blood sampling at 7 timepoints over 24 hours, with AUC constructed after calibrating serial drug levels.	Baseline, between week 16-32

Collaborators and Investigators

• Sponsor: National Taiwan University Clinical Trial Center

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 12, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: human immunodeficiency virus; metabolic dysfunction associated steatotic liver disease; tirzepatdie
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Glucose Metabolism Disorders; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; Insulin Resistance; Hyperinsulinism; Lipid Metabolism Disorders; HIV Infections; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Acquired Immunodeficiency Syndrome; Metabolic Syndrome; Diabetes Mellitus; Dyslipidemias; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 202604096MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes