Change in Body Weight and BMI in PWH with DOR/3TC/TDF Compared with INSTI

NCT06602622 | Recruiting Phase 4 DMC

• 1 other identifier: R-2024-3502-205
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 2

Brief Summary

Patients who developed metabolic syndrome after initiation of HIV treatment or with antiretroviral therapy (ART) for at least 36 months, treated with second generation integrase inhibitors (BIC/TAF/FTC, DTG/ABC/3Tc or DTG+TDF/FTC) who have gained at least 10% of their total body weight after starting ART, with a body mass index ≥25 kg/m2 and body fat greater than 20% will be eligible to participate in this clinical trial. If they decide to participate, they will sign an informed consent. After this, a mobile application will randomly decide whether the participant will continue with their ART regimen or switch to another ART (listed in the guidelines as one of the main lines of treatment) containing doravirine/lamivudine/disoproxil fumarate tenofovir. Medical visits will be at 1 month, 3 months, 6 months, 9 months, and 12 months after get in to this protocol, with laboratory studies that evaluate fats, blood sugar, liver function, kidney function, and test for HIV control; in addition, each visit will be given self-fillable scales to evaluate neuropsychiatric disorders such as depression, anxiety, insomnia, satisfaction with treatment or symptoms associated with it.The aim of the study is to observe whether there is weight loss with the change in HIV treatment.

Conditions

HIV; HIV Associate Weight Loss; HIV-1 Infection; Integrase Inhibitors, HIV; HIV PROTEASE INHIB; Weight Change; Weight Loss

Keywords

HIV; Integrase inhibitors; doravirine; Body Mass Index; Body Weight Changes

Outcome Measures

Primary Outcomes (1)

• Change in body weight and BMI

  To determine the percentage change in body weight and BMI in virologically suppressed PLHIV maintaining a second-generation INSTI regimen compared with those switching to DOR/3TC/TDF at 48 weeks post-switch. This will be measured with with the same scale at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.

  48 weeks

Secondary Outcomes (6)

• Adverse events

  48 weeks

• Evaluate neuropsychiatric disorders

  48 weeks

• Changes in lipid profile

  48 weeks

• Analyze changes in body composition

  48 weeks

• Cardiovascular risk

  48 weeks

Other Outcomes (2)

• HIVSDM scale symptom distress scale

  48 weeks

• HIV Treatment Satisfaction Questionnaire (HIVTSQ)

  48 weeks

Study Arms (2)

Integrase inhibitors

ACTIVE COMPARATOR

Second generation integrase inhibitor: 1) Bictegravir 50 mg/ alafenamide tenofovir 25 mg/ emtricitabine 200 mg (BIC/TAF/FTC) 2) Dolutegravir 50 mg/ abacavir 600 mg/ lamivudine 300 mg (DTG/ABC/3TC) or ) dolutegravir 50 mg+ disoproxil fumarate tenofovir/ emtricitabine 300mg/ 200 mg (DTG+TDF/FTC) Each will be prescribed one tablet every day during 48 weeks

Drug: Integrase inhibitor

DOR/TDF/3TC

EXPERIMENTAL

Individuals who meet the selection criteria will be randomized to maintain their same regimen with second-generation integrase inhibitors or switch to Doravirine/Tenofovir Disoproxil Fumarate/Emtricitabine 100/300/300 mg (DOR/TDF/3TC) It will be prescribed one tablet every day during 48 weeks

Drug: Doravirine + tenofovir DF + lamivudine

Interventions

Integrase inhibitor DRUG

Second generation integrase inhibitor 1) Bictegravir 50 mg/ alafenamide tenofovir 25 mg/ emtricitabine 200 mg (BIC/TAF/FTC); 2) Dolutegravir 50 mg/ abacavir 600 mg/ lamivudine 300 mg (DTG/ABC/3TC); 3) DTG 50mg+TDF 300mg/FTC 200mg (DTG+TDF/FTC) Each will be prescribed one tablet every day during 48 weeks

Integrase inhibitors

Doravirine + tenofovir DF + lamivudine DRUG

Individuals who meet the selection criteria will be randomized to maintain their same regimen with second-generation integrase inhibitors or switch to DOR/TDF/3TC 100/ 300/300 mg It will be prescribed one tablet every day during 48 weeks

DOR/TDF/3TC

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Virologically suppressed for at least 48 weeks prior to study entry
• Coming from a regimen containing Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF), Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC), or, Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine (DTG+TDF/FTC) with no known failures to integrase inhibitors for al least 48 weeks.
• BMI ≥25 kg/m2 at screening and
• Unintentional weight gain of \>10% from baseline (prior to INSTI initiation) within 1-3 years of starting INSTI ART, with no other apparent medical reason to explain the weight gain (concomitant medication use, Cushing's disease, recent prolonged hospitalization, etc.), in the opinion of the site investigator.
• Body fat percentage \>20%
• No indication or plans to add or change medications associated with significant weight change during the study period.
• Participants currently receiving antipsychotics, antidepressants, anticonvulsants/mood stabilizers, and thyroid replacement hormones without dose modifications for at least 12 weeks prior to randomization
• Participants currently receiving antidiabetics known to cause weight loss and without dose modifications for at least 24 weeks prior to randomization (GLP-1 receptor agonists, SGLT-2 inhibitors, insulin, metformin).
• Agree to adhere to assigned ART during the study period
• HIV-1 RNA screening \<50 copies/mL performed within 45 days prior to study entry.
• GFR by CDK-EPI ≥60 mL/min
• Alanine aminotransferase (ALT) and asparatate aminotransferase (AST) \< 90 IU/L
• Thyroid profile (TSH, free T3 and free T4) prior to entering the study
• Serum and urinary electrolytes, cystatin C, prior to entering the study

You may not qualify if:

• Loss of social security
• Allergy to any of the components of ART, previously unknown.
• Withdrawal of informed consent
• Acquiring HBV and/or HCV infection during follow-up.
• HIV-1 RNA \>200 copies/mL in 2 consecutive determinations after having achieved virological suppression.
• Early initiation or discontinuation of any of the following drugs after entering the study: antipsychotics (clozapine, olanzapine, risperidone); antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors) monoamine oxidase inhibitors, associated with weight gain; anticonvulsants/mood stabilizers (lithium, valproic acid) or associated with weight loss (topiramate); thyroid replacement hormones;
• Change in dose or discontinuation of antidiabetic drugs that cause weight loss (GLP-1 receptor agonists, SGLT-2 inhibitors, insulin, metformin), after entering the study.
• Planning to undergo or having undergone bariatric surgery.
• Initiating significant dietary changes, advised by a nutritionist according to what was reported by the participant
• Initiating or increasing physical exercise or enrolling in a structured weight loss regimen: \<250 minutes/week of moderate to intense activity

Sponsors & Collaborators

• Instituto Mexicano del Seguro Social: lead

Study Sites (2)

Hospital de infectología, Centro Médico Nacional La Raza

Mexico City, Azcapotzalco, 02990, Mexico

RECRUITING

Hospital de infectología, Centro Médico Nacional La Raza

Mexico City, Azcapotzalco, 02990, Mexico

RECRUITING

Related Publications (11)

• O'Halloran JA, Sahrmann J, Parra-Rodriguez L, Vo DT, Butler AM, Olsen MA, Powderly WG. Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Dec 19;75(12):2060-2065. doi: 10.1093/cid/ciac355.

  PMID: 35521785 BACKGROUND

• Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, Kaplan R, Lupinacci L, Rodgers A, Xu X, Lin G, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C, Martin EA; DRIVE-AHEAD Study Group. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019 Feb 1;68(4):535-544. doi: 10.1093/cid/ciy540.

  PMID: 30184165 BACKGROUND

• Calza L, Giglia M, Colangeli V, Bon I, Vitale S, Viale P. Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain. HIV Med. 2024 Aug;25(8):919-926. doi: 10.1111/hiv.13644. Epub 2024 Apr 3.

  PMID: 38570897 BACKGROUND

• Orkin C, Elion R, Thompson M, Rockstroh JK, Alvarez Bognar F, Xu ZJ, Hwang C, Sklar P, Martin EA. Changes in weight and BMI with first-line doravirine-based therapy. AIDS. 2021 Jan 1;35(1):91-99. doi: 10.1097/QAD.0000000000002725.

  PMID: 33048879 BACKGROUND

• Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.

  PMID: 29592840 BACKGROUND

• Bares SH, Wu X, Tassiopoulos K, Lake JE, Koletar SL, Kalayjian R, Erlandson KM. Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease. Clin Infect Dis. 2024 Feb 17;78(2):395-401. doi: 10.1093/cid/ciad545.

  PMID: 37698083 BACKGROUND

• Sokhela S, Venter WDF, Bosch B, Woods J, McCann K, Akpomiemie G, Chandiwana N, Mashabane N, Tembo A, Simmons B, Lalla-Edward S, Siedner MJ, Sinxadi P, Hermans L, Fairlie L, Vos A, Abrams E, Manne-Goehler JM, Moorhouse M, Clayden P, Norris S, Qavi A, Chersich M, Masenya M, Arulappan N, Hill A. Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens. Open Forum Infect Dis. 2024 Jan 24;11(3):ofae007. doi: 10.1093/ofid/ofae007. eCollection 2024 Mar.

  PMID: 38529213 BACKGROUND

• Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: Pathophysiology and Management. J Am Coll Cardiol. 2018 Jan 2;71(1):69-84. doi: 10.1016/j.jacc.2017.11.011.

  PMID: 29301630 BACKGROUND

• Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020 Feb;33(1):10-19. doi: 10.1097/QCO.0000000000000616.

  PMID: 31789693 BACKGROUND

• Hogg RS, Eyawo O, Collins AB, Zhang W, Jabbari S, Hull MW, Lima VD, Ahmed T, Kendall CE, Althoff KN, Justice AC, Barrios R, Shoveller J, Montaner JSG; Comparative Outcomes And Service Utilization Trends (COAST) study. Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study. Lancet HIV. 2017 Jun;4(6):e270-e276. doi: 10.1016/S2352-3018(17)30029-2. Epub 2017 Mar 3.

  PMID: 28262574 BACKGROUND

• Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020 Jun 1;3(6):e207954. doi: 10.1001/jamanetworkopen.2020.7954.

  PMID: 32539152 BACKGROUND

MeSH Terms

Conditions

Body Weight Changes; Weight Loss

Interventions

Integrase Inhibitors; doravirine; Tenofovir; Lamivudine

Condition Hierarchy (Ancestors)

Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Central Study Contacts

Ana L Cano, Postgraduate

CONTACT

2291243665; ana.knodiaz@gmail.com

José A Mata, Doctor

CONTACT

5530379053; jamatamarin@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Open label, randomized, clinical trial. Individuals who meet the inclusion criteria will be randomized to maintain their integrase inhibitor regimen (BIC/TAF/FTC, DTG/ABC/3TC or DTG+TDF/FTC) or to DOR/TDF/3TC.

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 19, 2024
• Study Start: August 14, 2024
• Primary Completion: November 14, 2025
• Study Completion: November 14, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ME (2)