DOR/TDF/3TC COmpared With BIC/FTC/TAF in ART-Naïve People Living With HIV and Overweight or Obesity
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-70
SponsorJosé Antonio Mata Marín
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Loss of social security coverage
Newly discovered allergy to study drugs
Withdrawal of consent
Hepatitis B or C infection acquired during follow-up
Trial design
Design model
Parallel
Treatments tested in this trial
DOR/3TC/TDF
DrugIt is a triple-drug antiretroviral drug co-formulated in a single tablet. It contains Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100/300/300 mg
BIC/FTC/TAF
DrugIt 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.
Treatment groups
306 Participants
are divided into 2 treatment groupsGroup A: BIC/TAF/FTCActive comparator 1 intervention
Group B: DOR/3TC/TDFExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
144 weeks2
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,
Time frame
144 weeks of follow-up with interim analysis at 48 and 96 weeksSecondary outcomes
1
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
Time frame
144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks2
To compare changes in body composition in PLWH treated with Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate versus Bictegravir/Emtricitabine/Tenofovir Alafenamide before initiating ART
Changes of percentage of fat
Time frame
144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks3
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
To compare changes in kidney function using cystatin C and creatinine levels calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation: Creatinine-Cystatin C expressed in ml/min/1.73 m2. Classifying kidney function stages: Stage 1: Normal (GFR \>90 ml/min/m2) Stage 2: Mild (GFR 60-89 ml/min/m2) Stage 3: Moderate (GFR 30-59 ml/min/m2) Stage 4: Severe (GFR 15-29 ml/min/m2) Stage 5: Renal failure for dialysis (GFR \<15 ml/min/m2)
Time frame
144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeks4
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
To evaluate and compare changes in cardiovascular risk based on the ASCVD (Atherosclerotic Cardiovascular Disease) 2013 Risk Calculator from American College of Cardiology (ACC) and American Heart Association in ART-naive PWH initiating DOR/3TC/TDF regimen compared with BIC/FTC/TAF after 144 weeks of follow-up. To evaluate in percentages of risk High cardiovascular risk: ≥20% Borderline cardiovascular risk: ≥5%-\<7.5% Low cardiovascular risk: \<5% The score is directly proportional to the risk, and determines the 10-year risk of ASCVD, (Atherosclerotic Cardiovascular Disease) for example: myocardial infarction, stroke, or death due to coronary heart disease or stroke
Time frame
144 weeks, with interim analyses at 24,48,72, 96 , 120, and 144 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
José Antonio Mata Marín
Lead sponsor
Instituto Mexicano del Seguro Social
Sponsor institution
Instituto Mexicano del Seguro Social
Collaborator
Source ClinicalTrials.gov