DOR/TDF/3TC COmpared With BIC/FTC/TAF in ART-Naïve People Living With HIV and Overweight or Obesity

NCT07075146 | Recruiting Phase 3 DMC

• 1 other identifier: R-2025-3502-101
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 1

Brief Summary

Background:Historically, HIV infection was associated with significant weight loss. However, weight gain is now commonly observed after initiating antiretroviral therapy (ART), particularly in individuals underweight at baseline. It remains unclear whether this weight gain reflects a "return to health" or results from drug-related or metabolic effects, and whether it persists beyond immune restoration. Recent evidence indicates that ART regimens containing second-generation integrase strand transfer inhibitors (INSTIs), such as bictegravir combined with tenofovir alafenamide, are associated with greater weight gain compared to other antiretroviral combinations, raising concerns about potential long-term metabolic consequences.Objective:To evaluate the effectiveness, safety, and tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) compared with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) in ART-naïve people living with HIV (PWH) who are overweight or obese.Materials and Methods:This open-label, randomized clinical trial, approved by the Ethics and Scientific Research Committee (No. 3502), will be conducted at the Infectious Diseases Hospital of the National Medical Center "La Raza" from May 2025 to May 2027. ART-naïve PWH, recently diagnosed, with no prior use of pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), who do not require hospitalization, and have a body mass index (BMI) ≥25 kg/m² and body fat \>20%, will be invited to participate. Participants will provide written informed consent and be randomized 1:1 to receive either DOR/3TC/TDF or BIC/FTC/TAF.

Conditions

HIV - Human Immunodeficiency Virus; Obesity; Overweight and/or Obesity

Keywords

HIV; overweight; obesity; Doravirine; Bictegravir

Outcome Measures

Primary Outcomes (2)

• To determine the safety and tolerability of Doravirine/Lamivudine/Tenofovir compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine in ART-naive people living with HIV at 144 weeks of treatment.

  Number of participants with treatment-related adverse events as assessed of serious adverse events (WHO grade 3 or 4) for PWH treated with DOR/TDF/3TC or BIC/FTC/TAF at 144 weeks, expressed in proportions of new cases.

  144 weeks

• Evaluate the effectiveness and safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) compared with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

  Effectiveness: Number of participants with viral load measurement (HIV-1 RNA) \<50 copies/mL at 144 weeks of follow-up for PWH treated with DOR/3TC/TDF or BIC/FTC/TAF,BIC/FTC/TAF at 144 weeks,

  144 weeks of follow-up with interim analysis at 48 and 96 weeks

Secondary Outcomes (4)

• To compare changes in lipid profile in people living with HIV (PLWH) treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide after initiating ART

  144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks

• To compare changes in body composition in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide before initiating ART

  144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks

• To compare changes in estimated glomerular filtration rate (eGFR) in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide after initiating TAR

  144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks

• To compare changes in cardiovascular risk using the Framingham Risk Score and the Pooled Cohort Equations (ASCVD AHA/ACC) in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide

  144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks

Study Arms (2)

BIC/TAF/FTC

ACTIVE COMPARATOR

Bictegravir/ tenofovir alafenamide/ emtricitabine 50/ 25/ 200 mg. It is the usual therapy, consisting of 3 drugs in a single tablet, based on an integrase inhibitor, and 2 nucleoside analogues, it is the experimental group

Drug: BIC/FTC/TAF

DOR/3TC/TDF

EXPERIMENTAL

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100/300/300 mg Non-nucleoside reverse transcriptase inhibitor (doravirine) Nucleoside reverse transcriptase inhibitors (lamivudine, tenofovir disoproxil fumarate)

Drug: DOR/3TC/TDF

Interventions

DOR/3TC/TDF DRUG

It is a triple-drug antiretroviral drug co-formulated in a single tablet. It contains Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100/300/300 mg

DOR/3TC/TDF

BIC/FTC/TAF DRUG

It is a triple-drug antiretroviral drug co-formulated in a single tablet. It contains bictegravir 50 mg, tenofovir alafenamide 25 mg, and emtricitabine 200 mg. It is the standard therapy.

BIC/TAF/FTC

Eligibility Criteria

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

You may qualify if:

• Adults (≥18 years) with confirmed HIV diagnosis, ART-naïve
• Signed informed consent
• HIV-1 RNA ≥1000 copies/mL
• No history of PrEP or PEP failure
• BMI ≥25 kg/m² and body fat \>20%
• Stable treatment for dyslipidemia (if applicable)
• No planned medication changes affecting weight
• Willingness to adhere to assigned ART
• Recent HIV-1 RNA and CD4+ results
• GFR (CKD-EPItip) ≥60 mL/min
• ALT and AST \<90 IU/L
• \. Uncontrolled diabetes 2. Recent changes in insulin or hypoglycemic drugs (\<3 months) 3. Active malignancy 4. History of bariatric surgery 5. Allergies to study drugs 6. Hepatitis B and/or C coinfection 7. GFR \<60 mL/min (CKD-EPI) 8. Drug interactions with ART regimens 9. Recent (60 days) use of anorectic drugs 10. Recent (30 days) hospitalization for severe illness 11. Unstable hypothyroidism

You may not qualify if:

• Loss of social security coverage
• Newly discovered allergy to study drugs
• Withdrawal of consent
• Hepatitis B or C infection acquired during follow-up
• Use of psychiatric or thyroid medications without a stable dose for ≥12 weeks
• Initiation or discontinuation of medications affecting weight after enrollment
• Unplanned bariatric surgery

Sponsors & Collaborators

• José Antonio Mata Marín: lead
• Instituto Mexicano del Seguro Social: collaborator

Study Sites (1)

Hospital de infectología, Centro Médico Nacional La Raza

Mexico City, 02990, Mexico

RECRUITING

Related Publications (2)

• Kousari AE, Wilson MP, Hawkins KL, Bandali MM, Henao-Martinez AF, Gardner EM, Erlandson KM. Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV. HIV Res Clin Pract. 2024 Dec;25(1):2339576. Epub 2024 Jun 3.

  PMID: 38831550 BACKGROUND

• Orkin C, Molina JM, Cahn P, Lombaard J, Supparatpinyo K, Kumar S, Campbell H, Wan H, Teal V, Jin Xu Z, Asante-Appiah E, Sklar P, Teppler H, Lahoulou R; DRIVE-FORWARD and DRIVE-AHEAD collaborators. Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials. Lancet HIV. 2024 Feb;11(2):e75-e85. doi: 10.1016/S2352-3018(23)00258-8. Epub 2023 Dec 20.

  PMID: 38141637 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Obesity; Overweight

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; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• José A Mata, M.Sc

  Instituto Mexicano del Seguro Social

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José A Mata, M.Sc

CONTACT

525530379053; jamatamarin@gmail.com

Paola E Padilla, Student

CONTACT

5527946030; paolaedith1b@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Model Details: Study design: Experimental, longitudinal, prospective, randomized 1:1, open-label. Study type: Open-label, randomized clinical trial. Study location: Infectious Diseases Hospital. Study duration: 144 weeks

Study Record Dates

• First Submitted: June 28, 2025
• First Posted: July 20, 2025
• Study Start: May 5, 2025
• Primary Completion (Estimated): June 5, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)