Can INSTI-associated Weight Gain be Halted or Reversed With a Switch to Doravirine/Lamivudine/Tenofovir DF?

NCT04665375 | Terminated Phase 4 Results

• 1 other identifier: 20-5228
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Weight gain with the integrase inhibitors and tenofovir alafenamide has been observed in observational cohorts and randomized controlled clinical trials. Although some risk factors have been identified, the cause is unknown and it remains to be determined if the changes are reversible. The weight gain is of concern to persons living with HIV. This pilot intervention study is designed to provide preliminary data on whether switching patients with weight gain on an INSTI-based regimen to a combination of doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/3TC/TDF, an NNRTI-based regimen) for one year can slow down or even reverse weight gain. These data will then be used to inform the design and sample size of a larger switch study.

Conditions

Hiv; Weight Gain

Keywords

weight gain; HIV; doravirine; integrase inhibitor; tenofovir alafenamide; tenofovir disoproxil fumarate

Outcome Measures

Primary Outcomes (4)

• Identify Number of Active Clinic Patients Who Completed the Study Protocol.

  The primary objective was to determine how many clinic patients with ≥10% weight gain on an INSTI would complete the study (48 weeks).

  1 year

• Identify Reasons for Study Ineligibility Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain.

  Descriptive data. Reasons for study ineligibility (i.e., not meeting inclusion criteria or presence of one or more exclusion criteria) will be recorded by the study coordinator.

  1 year

• Identify Reasons for Study Refusal Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain.

  Descriptive data. Clinic patients who refuse to participate in the study will be asked an open-ended question by the study coordinator about main reason(s) for declining. Responses will be grouped by the following categories: fear of side effects, distrust of researchers, general concerns about research design, interference in everyday life or changes in routine, and social discrimination.

  1 year

• Identify Factors Associated With Early Study Discontinuation.

  Factors will include age, gender, race, CD4 count, HIV viral load, prior enrollment in a study, history of injection drug use, and use of antidepressants.

  1 year

Secondary Outcomes (6)

• To Determine the Change in Absolute Weight From Baseline to One Year Following the Switch to DOR/TDF/3TC.

  1 year

• Number of Participants Who Experienced a Change in Weight After a Switch to DOR/TDF/3TC at 1 Year

  1 year

• Change in Waist Circumference From Baseline to One Year Following the Switch to DOR/TDF/3TC.

  1 year

• Number of Participants Who Experienced a Change in BMI Category After a Switch to DOR/TDF/3TC at One Year

  1 year

• Number of Participants Who Maintain HIV RNA<50 Copies/mL After a Switch to DOR/TDF/3TC at 1 Year

  1 year

Other Outcomes (6)

• Loss of Percentage of Total Body Fat From Baseline to One Year

  1 year

• Change in Self-esteem Related to Body Image as Per the Body Image Questionnaire B-WISE at One Year Versus Baseline.

  1 year

• To Determine the Change in Perceived Changes in Body Size as Per the FRAM Body Image Questionnaire

  1 year

Study Arms (1)

DOR/3TC/TDF

EXPERIMENTAL

100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF)

Drug: DOR/3TC/TDF

Interventions

DOR/3TC/TDF DRUG

switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year

Also known as: Delstrigo

DOR/3TC/TDF

Eligibility Criteria

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

You may qualify if:

• Documented HIV-1 infection by means of any one of the following:
• Documentation of HIV diagnosis in the medical record by a licensed health care provider; OR HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating \>1000 RNA copies/mL; OR any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid Multispot antibody differentiation assay.
• On an Integrase Strand Transfer Inhibitor (INSTI) based regimen for at least 1 year and less than 5 years prior to screening
• Significant weight gain since initiation of the INSTI-based regimen (\>10% of baseline body weight)
• Viral load of \<200 copies/mL for \> 6 consecutive months prior to screening (single viral blips \<200 copies/mL accepted if re-suppressed)
• Documentation of weight, glycemia, cholesterol, and blood pressure (BP) history within the last year.
• Signed Informed Consent Form (Appendix B) and willing to comply with the protocol.
• Using proper contraception if of child bearing age and potential.

You may not qualify if:

• Pregnancy or desire to become pregnant within the next year
• Failure to use adequate contraception during the study if of child-bearing potential.
• Any underlying documented ART resistance to doravirine, tenofovir disoproxil fumarate, or lamivudine
• Prior virologic failure
• Concomitant drugs that interact with doravirine
• Initiated on concomitant drugs known to cause weight gain within the last 6 months (i.e. antidepressants and antipsychotics)
• Concomitant drugs known to cause nephrotoxicity
• History of renal toxicity or renal events while on TDF therapy.
• Creatinine clearance (CrCL) \< 50 mL/min
• Inability to read/understand English

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Merck Canada Inc.: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G2C4, Canada

Location

Related Publications (15)

• Lakey W, Yang LY, Yancy W, Chow SC, Hicks C. Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons. AIDS Res Hum Retroviruses. 2013 Mar;29(3):435-40. doi: 10.1089/aid.2012.0234. Epub 2012 Nov 7.

  PMID: 23072344 BACKGROUND

• Kumar S, Samaras K. The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality. Front Endocrinol (Lausanne). 2018 Nov 27;9:705. doi: 10.3389/fendo.2018.00705. eCollection 2018.

  PMID: 30542325 BACKGROUND

• Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, Norris S, Chersich M, Clayden P, Abrams E, Arulappan N, Vos A, McCann K, Simmons B, Hill A. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med. 2019 Aug 29;381(9):803-815. doi: 10.1056/NEJMoa1902824. Epub 2019 Jul 24.

  PMID: 31339677 BACKGROUND

• Gomez M, Seybold U, Roider J, Harter G, Bogner JR. Correction to: A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015-2017. Infection. 2019 Feb;47(1):103-104. doi: 10.1007/s15010-018-1251-0.

  PMID: 30456685 BACKGROUND

• Reynes J, Trinh R, Pulido F, Soto-Malave R, Gathe J, Qaqish R, Tian M, Fredrick L, Podsadecki T, Norton M, Nilius A. Lopinavir/ritonavir combined with raltegravir or tenofovir/emtricitabine in antiretroviral-naive subjects: 96-week results of the PROGRESS study. AIDS Res Hum Retroviruses. 2013 Feb;29(2):256-65. doi: 10.1089/aid.2011.0275. Epub 2012 Aug 3.

  PMID: 22730929 BACKGROUND

• Rockstroh JK, Lennox JL, Dejesus E, Saag MS, Lazzarin A, Wan H, Walker ML, Xu X, Zhao J, Teppler H, Dinubile MJ, Rodgers AJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK Investigators. Long-term treatment with raltegravir or efavirenz combined with tenofovir/emtricitabine for treatment-naive human immunodeficiency virus-1-infected patients: 156-week results from STARTMRK. Clin Infect Dis. 2011 Oct;53(8):807-16. doi: 10.1093/cid/cir510.

  PMID: 21921224 BACKGROUND

• McCann K, Moorhouse M, Sokhela S, Venter WD, Serenata C, Qavi A, et al. Changes in DXA-assessed body composition in TAF/FTC+DTG compared to TDF/FTC+DTG and TDF/FTC/EFV in the ADVANCE clinical trial. EACS, November 6-9, 2019, Basel, Switzerland.

  BACKGROUND

• Bedimo R, Li X, Adams-Huet B, Lake J, Taylor B, Kim D, et al. Differential BMI changes following PI- and INSTI-based ART initiation by sex and race. Conference on Retroviruses and Opportunistic Infections; 2019 Mar 4-7; Seattle, Washington

  BACKGROUND

• Rebeiro P, Jenkins C, Bian A, Lake J, Bourgi K, Horberg M, et al. The effect of initiating integrase inhibitor-based vs. non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy on progression to diabetes among North American persons in HIV care. IDWeek, October 2-6, 2019, Washington, DC. Abstract LB9.

  BACKGROUND

• Schafer J, Sassa K, O'Connor J, Shimada A, Keith S, DeSimone J. BMI and ASCVD risk score changes in virologically suppressed patients with HIV switching from TDF to TAF containing ART. IDWeek, October 2-6, 2019, Washington, DC. Abstract 979

  BACKGROUND

• Kerchberger AM, Sheth AN, Angert CD, Mehta CC, Summers NA, Ofotokun I, et al. Integrase Strand Transfer Inhibitors are Associated with Weight Gain in Women. CROI, March 4-7, 2019, Seattle, DC. Abstract 672.

  BACKGROUND

• Johnson M, Kumar P, Molina JM, Rizzardini G, Cahn P, Bickel M, Mallolas J, Zhou Y, Morais C, Kumar S, Sklar P, Hanna GJ, Hwang C, Greaves W; DRIVE-SHIFT Study Group. Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial. J Acquir Immune Defic Syndr. 2019 Aug 1;81(4):463-472. doi: 10.1097/QAI.0000000000002056.

  PMID: 30985556 BACKGROUND

• Hill A, Hughes SL, Gotham D, Pozniak AL. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety? J Virus Erad. 2018 Apr 1;4(2):72-79. doi: 10.1016/S2055-6640(20)30248-X.

  PMID: 29682298 BACKGROUND

• Andersen JW, Fass R, van der Horst C. Factors associated with early study discontinuation in AACTG studies, DACS 200. Contemp Clin Trials. 2007 Sep;28(5):583-92. doi: 10.1016/j.cct.2007.02.002. Epub 2007 Feb 27.

  PMID: 17395549 BACKGROUND

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed [October 30, 2019].

  BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Weight Gain

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Sharon Walmsley
• Organization: University Health Network

sharon.walmsley@uhn.ca

416-340-5077

Study Officials

• Sharon Walmsley

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot intervention study

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 11, 2020
• Study Start: April 26, 2021
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: July 16, 2025
• Results First Posted: July 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)