Doravirine for Obese Persons on Integrase Inhibitors and Tenofovir Alafenamide

NCT04636437 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: ACTG A5391UM1AI068636
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 27

Brief Summary

The purpose of this study was to determine if people with HIV and obesity taking an antiretroviral treatment regimen containing an integrase strand transfer inhibitor (INSTI) with (tenofovir alafenamide/emtricitabine (TAF/FTC) would either slow their rate of weight gain, or even lose weight, over the span of about 1 year after a switch to a regimen containing doravirine (DOR; a newer, non-nucleoside reverse transcriptase inhibitor medication) combined with either TAF/TFC or tenofovir disoproxil fumarate (TDF)/FTC.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Mean Change (Percent) in Body Weight (kg) From Entry to Week 48

  The percentage change is defined as weight at week 48 minus weight at entry, then divided by weight at entry, then multiplied by 100. Mean and confidence interval (CI) come from a linear regression model adjusting for entry weight, sex, and race (Black and not Black).

  Entry to week 48

Secondary Outcomes (26)

• Mean Change (Percent) in Body Weight (kg) From Entry to Week 24

  Entry to week 24

• Mean Change (Absolute) in Waist Circumference From Entry to Week 48

  Entry to week 48

• Mean Change (Absolute) in Waist Circumference From Entry to Week 24

  Entry to week 24

• Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 48

  Entry to week 48

• Mean Change (Absolute) in Fasting Triglycerides From Entry to Week 24

  Entry to week 24

Study Arms (3)

DOR 100 mg + TAF/FTC

EXPERIMENTAL

By mouth daily with or without food

Drug: Doravirine 100 Mg; Drug: Integrase strand transfer inhibitors

DOR 100 mg + TDF/FTC

EXPERIMENTAL

By mouth daily with or without food

Drug: Doravirine 100 Mg; Drug: tenofovir disproxil fumarate/emtricitabine

Continuation of INSTI+TAF/FTC

ACTIVE COMPARATOR

By mouth daily with or without food

Drug: Integrase strand transfer inhibitors; Drug: Tenofovir alafenamide/emtricitabine

Interventions

Doravirine 100 Mg DRUG

Participants received a 100 mg tablet by mouth daily with or without food.

Also known as: DOR

DOR 100 mg + TAF/FTC; DOR 100 mg + TDF/FTC

Integrase strand transfer inhibitors DRUG

INSTIs were acquired through the standard of care locally.

Also known as: INSTI

Continuation of INSTI+TAF/FTC; DOR 100 mg + TAF/FTC

Tenofovir alafenamide/emtricitabine DRUG

NRTIs (TAF/FTC) were acquired through the standard of care locally.

Also known as: TAF, FTC

Continuation of INSTI+TAF/FTC

tenofovir disproxil fumarate/emtricitabine DRUG

NRTIs (TDF/FTC) were acquired through the standard of care locally.

Also known as: TDF, FTC

DOR 100 mg + TDF/FTC

Eligibility Criteria

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

You may qualify if:

• Ability and willingness of participant or legal guardian/representative to provide informed consent.
• HIV-1, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load. If a rapid HIV test or any FDA-approved HIV-1 E/CIA test kit is not available, two HIV-1 RNA values ≥2000 copies/mL at least 24 hours apart may be performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or by any non-US laboratory that is DAIDS Good Clinical Laboratory Practice (GCLP) compliant and, if performing HIV-1 RNA testing, is Virology Quality Assurance (VQA)-certified.
• Currently on a bictegravir (BIC), dolutegravir (DTG), or raltegravir (RAL) + TAF/FTC regimen with ≥48 weeks prior to study entry.
• Ability to acquire NRTIs (TAF/FTC or TDF/FTC) and INSTI through usual care for the duration of the study.
• A BMI ≥30 kg/m2 at screening. No known plans to change or to initiate medications known to be associated with significant weight changes during study period.
• Agree to adhere to assigned ART during the study period At least one HIV-1 RNA level \<50 copies/mL (or below the lower limit of HIV-1 RNA detection available at the site if the lower limit of detection is \>50) performed in the 48 weeks prior (≤48 weeks) to study screening, and at least one HIV-1 RNA level \<50 copies/mL ≥48 weeks prior to study screening, using an FDA-approved assay performed by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
• Screening HIV-1 RNA \<50 copies/mL (or below the lower limit of HIV-1 RNA detection available if the lower limit of detection is \>50) performed within 45 days prior to study entry by any US laboratory that possesses a CLIA certification or its equivalent, or at any network-approved non-US laboratory that is VQA certified.
• For participants capable of becoming pregnant, negative serum or urine pregnancy test within 45 days prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.
• Participants engaging in sexual activity and capable of becoming pregnant must agree to use contraception while on study drug (approximately 48 weeks) and for 8 weeks after the end of the study. At least one of the following contraceptive methods must be used:
• Intrauterine device (IUD)
• Hormone-based contraceptive
• Partner sterilization (i.e., vasectomy) and is the sole partner for the participant.
• Transgender participants who are currently taking hormones must be on a stable hormone dose for \>12 weeks prior to study entry. Transgender participants should not have active plans to change their hormone regimen or dose during the study period.
• The following laboratory values obtained within 45 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
• Absolute neutrophil count (ANC) \>750 cells/mm3

You may not qualify if:

• Historical or current evidence of the K65R/E/N or M184V/I mutations (for participants who have undergone HIV-1 genotyping), due to the potential for viral rebound after switch from an INSTI- to NNRTI-based regimen.
• Historical or current evidence of major mutations associated with NNRTI resistance.
• History of prior virologic failure in the opinion of the site investigator. For example, a confirmed plasma HIV-1 RNA \>1000 copies/mL after having achieved viral suppression.
• Prior exposure to single-dose nevirapine for the prevention of parent-to-child transmission of HIV.
• Any history of significant renal toxicity while taking TDF (as determined by the site investigator).
• Currently breast-feeding or pregnant, or intending to become pregnant during the duration of the study.
• Current use, use in the 4 weeks preceding study entry, or anticipated use of prohibited drugs during the study period.
• Anticipated start or cessation of any of the following drugs during the study period:
• Antipsychotics (e.g., clozapine, olanzapine, risperidone, etc.) and antidepressants (tricyclic antidepressants, e.g., amitriptyline, nortriptyline, etc.; selective serotonin reuptake inhibitors, e.g., fluoxetine, paroxetine, sertraline, etc.; and monoamine oxidase inhibitors, e.g., selegiline) associated with weight gain
• Anticonvulsants/mood stabilizers associated with weight gain (e.g., lithium, valproic acid) or weight loss (e.g., topiramate)
• Thyroid replacement hormones
• Anti-diabetic agents known to cause weight loss (e.g., GLP-1 receptor agonists such as exenatide, dulaglutide, semaglutide, metformin, and SGLT-2 inhibitors such as canagliflozin, dapagliflozin, etc.).
• Planning to undergo bariatric surgery or initiate significant dietary or exercise changes within the study period (e.g., structured weight loss programs such as Weight Watchers), as determined by participant report.
• Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with ability to adhere to study requirements, or cessation of regular methamphetamine use, as determined by the site investigator, within 60 days prior to study entry.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (27)

Alabama CRS (31788)

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

UCSD Antiviral Research Center CRS (701)

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs (801)

San Francisco, California, 94110, United States

Location

Harbor-UCLA CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Whitman-Walker Institute, Inc. CRS (31791)

Washington D.C., District of Columbia, 20005, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University CRS (201)

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital (MGH) CRS (101)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, 02115, United States

Location

Washington University Therapeutics (WT) CRS (2101)

St Louis, Missouri, 63110, United States

Location

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS (7804)

New York, New York, 10010, United States

Location

Columbia Physicians and Surgeons (P&S) CRS (30329)

New York, New York, 10032, United States

Location

Weill Cornell Upton CRS (7803)

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, 14642, United States

Location

Chapel Hill CRS (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS (2301)

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Therapeutics (VT) CRS (3652)

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

University of Washington Positive Research CRS (1401)

Seattle, Washington, 98104, United States

Location

Related Links

• Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)
• Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0 - January 2010)
• CKD-EPI Creatinine Equation (2021)

MeSH Terms

Conditions

HIV Infections

Interventions

doravirine; emtricitabine tenofovir alafenamide; Racivir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• John Koethe

  Vanderbilt University Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: November 19, 2020
• Study Start: July 27, 2021
• Primary Completion: October 18, 2024
• Study Completion: October 18, 2024
• Last Updated: July 2, 2025
• Results First Posted: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? To achieve aims in the proposal approved by the ACTG. * By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data."

Locations

US (27)