Effect of Biktarvy & Symtuza on microRNAs in HIV and Correlation With Weight Gain

Effect of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide and Bictegravir/Emtricitabine/Tenofovir Alafenamide on the Circulatory microRNA Profile in Treatment naïve HIV Patients, and Its Correlation With Change in Body Weight

The purpose of this research study is to understand why certain HIV medication regimens (called anti-retroviral or ARV medications) cause more weight gain than others. In this research, the investigators will compare micro-RNA profiles of people who take Symtuza(darunavir(D)/cobicistat(C)/emtricitabine(F)/tenofovir alafenamide (TAF))[D/C/F/TAF] with those who take Biktarvy(bictegravir(B)/emtricitabine(F)/tenofovir alafenamide (TAF))[B/F/TAF] and try to correlate this with the change in body weight and BMI over a course of 48 weeks. The investigators will also attempt to monitor the calorie intake of the participants in the two groups and correlate it with treatment-induced weight gain. Micro-RNAs are small molecules that are produced naturally in the human body, and which are responsible for modifying the expressions of genes. They have the potential to be used in diagnostic and therapeutic medicine and their putative role has been explored in many diseases across many clinical trials. By doing this research, the investigators hope to learn more about their role in HIV disease and its correlation with treatment-induced weight gain.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; Obesity
• Intervention / Treatment: Drug: Biktarvy; Drug: Symtuza

Detailed Description

With advances in HIV treatment, the life expectancy of persons with HIV (PWH) has improved and complications associated with antiretroviral (ARV) medications have become more apparent. Among them, weight gain and obesity, because of their associated complications, is one of the more concerning ones. Certain drug regimens are more adipogenic than others, but not a lot is known about molecular mechanisms responsible for these differences. Micro RNAs (miRNAs) are small non-coding RNAs that control gene expression and regulate a wide array of biological processes. In recent years miRNAs have been studied in a number of diseases for diagnostic and even therapeutic purposes. There are studies showing differences in miRNA profiles in obese vs non-obese non-HIV population, as well as certain miRNAs as biomarkers of response to weight-loss diets. In PWH, there are studies that looked at the effect of HIV infection on the miRNA profile and how a particular miRNA profile is predictive of ARV resistance. But there are no studies that specifically looked at how ARV medications alter the miRNA profile and how (in terms of miRNA profiles) one combination is more adipogenic than the other.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Paul Cook, MD; Phone Number: 252-744-4500; Email: cookp@ecu.edu
• Study Contact Backup: Name: Smit Rajput, MD; Phone Number: 252-744-2574; Email: rajputs20@ecu.edu

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Recruiting
      • Adult Specialty Care Clinic-East Carolina University
      • Contact: Jamie Wigent, RN; Phone Number: 252-414-2655; Email: wigentj17@ecu.edu
      • Contact: Allison Geigel, RN; Phone Number: 252-414-2655; Email: geigela20@ecu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects age >/=18 years
2. HIV infection with HIV RNA >/= 1000 copies/ml of plasma
3. Treatment naïve
4. Have access to a smartphone with internet access
5. Willing to provide written informed consent.

Exclusion Criteria:

1. Morbid obesity (BMI>/=40) or cachexia (BMI=/<20)
2. Known or suspected active substance abuse that in the opinion of the investigator would impact study participation
3. On medications associated with weight loss or gain, including insulin, glucagon-like peptide(GLP)-1 analogs, anti-depressants, antipsychotics, corticosteroids, orlistat
4. Bedbound due to other chronic conditions
5. Pregnant females
6. Prisoners
7. Unwilling or unable to comply with protocol requirements.
8. On medication known to interact significantly with any of the components of Symtuza or Biktarvy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biktarvy; 15 subjects will get Biktarvy (single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide) once daily.	Drug: Biktarvy; microRNA profiles of subjects on Biktarvy, will be compared with those who are on Symtuza, at various time points.; Other Names: bictegravir/emtricitabine/tenofovir alafenamide
Experimental: Symtuza; 15 subjects will get Symtuza (single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide) once daily.	Drug: Symtuza; microRNA profiles of subjects on Symtuza, will be compared with those who are on Biktarvy, at various time points.; Other Names: darunavir/cobicistat/emtricitabine/tenofovir alafenamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Body mass index-BMI(kg/m^2) of the participants	Weight(in kilograms or kg) and height(in meters or m) will be combined to report BMI in kg/m^2	48 weeks
miRNA(microRNA) profiles of the two groups	we will monitor microRNAs of the two groups	48 weeks
Change from baseline in body weight(in kilograms or kg) of the participants	we will monitor change in body weight & BMI	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calorie intake of subjects in the two groups.	we will monitor calorie intake of subjects in two grouos	48 weeks

Collaborators and Investigators

• Sponsor: East Carolina University
• Collaborators: Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Paul Cook, MD, East Carolina University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: microRNA; miRNA; ARV; Antiretroviral medications
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Cobicistat; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Darunavir; Cobicistat mixture with darunavir
• Other Study ID Numbers: UMCIRB 22-000833

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.: No