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

NCT04820933 | Completed Early Phase 1 FDA Drug

• 1 other identifier: MISP# 60720 ; STU-2023-0724
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Lipid Metabolism Disorders; HIV I Infection; Cardiovascular Risk Factor

Keywords

HIV; Antiretroviral therapy; Cardiovascular disease

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Total cholesterol

  12 weeks post switch of antivirals

Study Arms (1)

Doravirine plus emtricitabine and tenofovir alafenamide fumarate

EXPERIMENTAL

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

Interventions

Doravirine 100 Mg DRUG

Doravirine 100 Mg orally dail

Also known as: Descovy (200 mg emtricitabine + 10 mg tenofovir alafenamide fumarate)

Doravirine plus emtricitabine and tenofovir alafenamide fumarate

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

University of Texas Southwestern Medical Center

Dallas, Texas, 75219, United States

Location

University of Texas Southwestern

Dallas, Texas, 75219, United States

Location

MeSH Terms

Conditions

Lipid Metabolism Disorders; Cardiovascular Diseases

Interventions

doravirine; emtricitabine tenofovir alafenamide; Emtricitabine

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Theodoros Kelesidis, MD PHD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 29, 2021
• Study Start: March 1, 2024
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)