Doravirine Versus Integrase Inhibitors on Backbone of Emtricitabine and Tenofovir Alafenamide in HIV

A Switch Clinical Trial of Antiretrovirals to Compare the Impact of Doravirine Versus Integrase Inhibitors With Backbone of Emtricitabine and Tenofovir Alafenamide on Instigators of Atherosclerosis in Persons With Chronic Treated HIV.

This research application will explore the impact of the Non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine in the setting of established Nucleoside reverse transcriptase inhibitors (NRTIs) backbone [Tenofovir alafenamide (TAF) / Emtricitabine (FTC) as a possible therapeutic strategy to minimize the detrimental impact of ART-related toxicities on metabolism and instigators of atherosclerosis. Given the possible favorable role of NNRTI in pathogenesis of HIV-related dyslipidemia and cardiovascular disease (CVD), this research will provide mechanistic insights into HIV pathogenesis and safety data regarding doravirine (DOR). These data may promote DOR as a robust "HDL friendly" and "metabolism friendly", therapeutic agent that may attenuate morbidity in chronic treated HIV infection. Towards this aim, the investigators will study DOR-related effects on HDL (HDL-C levels and function) and ex vivo assays that determine key molecular determinants of atherogenesis.

Study Overview

• Status: Completed
• Conditions: Lipid Metabolism Disorders; Cardiovascular Risk Factor; HIV I Infection
• Intervention / Treatment: Drug: Doravirine 100 Mg

Detailed Description

Aim 1: To evaluate the relative in vivo impact of DOR on independent measures of HDL function (antioxidant function, cholesterol efflux) compared to integrase inhibitors (raltegravir, dolutegravir, elvitegravir, bictegravir) in the setting of TAF backbone in HIV infected persons with dyslipidemia.

Aim 2: To evaluate the relative in vivo impact of DOR on ex vivo atherogenesis (monocyte-derived foam cell efflux and chemotaxis) compared to integrase inhibitors (raltegravir, dolutegravir, elvitegravir, bictegravir) in the setting of TAF backbone.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75219
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75219
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older
• Cases: Chronically infected and on anti-retroviral therapy with suppressed viremia for at least 3 months (viral RNA <50 copies per ml)
• On stable antiretroviral therapy for >6 months with Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg; E/C/F/TAF) 2) Biktarvy (bictegravir 50 mg/ emtricitabine 200 mg/tenofovir alafenamide 25 mg; B/F/TAF).
• Dyslipidemia (Defined based on use of lipid lowering medications or abnormal baseline lipids (total cholesterol, triglycerides, high density lipoprotein): Rationale: Enrolling participants with dyslipidemia will determine whether switching from TAF/FTC/integrase inhibitor regimen to TAF/FTC/doravirine regimen will directly improve the lipids over 3 months within the same participant.
• Adequate renal function determined by the Cockcroft-Gault formula for creatinine clearance (>60 mL/min/1.73 m2
• Able and willing to provide written consent

Exclusion Criteria:

• • Pregnancy

  • Hepatitis; no evidence of acute hepatitis in the prior 30 days
  • History of severe renal impairment (eGFR < 30 ml/min/1.73 m2)
  • History of severe or recent cardiac event
  • Current alcoholism or IV drug abuse
  • Use of systemic immunomodulatory medications (e.g. steroids) within 4 weeks of enrollment
  • Anemia precluding safe donation of blood (For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100 ml and in women as hemoglobin of less than 12.0 gram/100 ml).
  • Use of any investigational products within 4 weeks of enrollment
  • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.
  • Subjects who are on medications that are strong inducers of CYP3A (as these may decrease the efficacy of Stribild or Genvoya). Examples include phenobarbital, phenytoin, carbamazepine, and rifampin.
  • Subjects who are on medications that are cleared by CYP3A and that may be toxic with elevated drug levels (examples include Cisapride, ergotamine, Pimozide, Lurasidone, Lovastatin, and Simvastatin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doravirine plus emtricitabine and tenofovir alafenamide fumarate; PIFELTRO (doravirine) 100 mg tablet one daily for 3 months Descovy (200 mg emtricitabine + 10 mg tenofovir alafenamide fumarate) tablet one daily for 3 months	Drug: Doravirine 100 Mg; Doravirine 100 Mg orally dail; Other Names: Descovy (200 mg emtricitabine + 10 mg tenofovir alafenamide fumarate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HDL function	Primary outcome (instigator of atherosclerosis). This is a measure of the lipid peroxide content of HDL per specific amount of HDL relative to the measure of this value in a pooled healthy control (normalized ratio; no units).	12 weeks post switch of antivirals
Monocyte chemotaxis	Primary outcome (instigator of atherosclerosis). This is a measure of the ability of isolated blood monocytes to migrate through a trans endothelial layer in an ex vivo model of atherogenesis. Units are % of monocytes that migrated (% chemotaxis).	12 weeks post switch of antivirals
Monocyte derived foam cell formation of monocytes	Primary outcome (instigator of atherosclerosis). This is a measure of the ability of isolated blood monocytes to take up lipids and form foam cells in an ex vivo model of atherogenesis. Units are % of monocytes that became foam cells (% Monocyte derived foam cell formation).	12 weeks post switch of antivirals

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total cholesterol	Secondary outcome (instigator of atherosclerosis). Units are mg/dl.	12 weeks post switch of antivirals

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Theodoros Kelesidis, MD PHD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): October 1, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular disease; HIV; Antiretroviral therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutritional and Metabolic Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Deoxyribonucleosides; Emtricitabine; doravirine; emtricitabine tenofovir alafenamide
• Other Study ID Numbers: MISP# 60720 ; STU-2023-0724

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