Safety, Tolerability and Effectiveness of DTG/3TC vs BIC/TAF/FTC in PWH Without Antiretroviral Experience
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstituto Mexicano del Seguro Social
About this trial
Background: The primary goal of antiretroviral therapy is to prevent HIV-associated morbidity and mortality. The effectiveness of first-line regimens is supported by a large number of clinical trials; current concerns focus on the long-term adverse effects of antiretrovirals, especially integrase strand transfer inhibitors, as they have been associated with significant weight gain, which may be associated with increased cardiovascular risk.
Objective: To determine the effectiveness, safety, and tolerability of Dolutegravir/Lamivudine (DTG/3TC) compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/TAF/FTC) in treatment-naive people living with HIV (PWH). Materials and methods: With prior approval from the Ethics and Scientific Research Committee 3502, an open-label, randomized clinical trial will be conducted at the Infectious Diseases Hospital of the National Medical Center "La Raza" from November 2024 to May 2026. Recently diagnosed PWH with no history of PrEP and/or PeP use, without hospitalization criteria, and without a diagnosis of metabolic syndrome based on ATP-III criteria will be identified. They will be invited to participate in the study and, if they accept, they will sign an informed consent form. They will be randomized to start a BIC/TAF/FTC or DTG/3TC 1:1 regimen. Laboratory studies, vital signs, and somatometry including bioimpedance will be performed at 4, 12, 24, 36, 48, 72, 96, 120, 144 weeks of follow-up; viral load and CD4+ count will be measured at weeks 12, 24, 48, 72, 96, 120, 144 weeks after the start of treatment. Sampling will be non-probabilistic; the distribution will be identified using the Kolmogorov-Smirnoff test, and measures of central tendency and percentages will be expressed. Comparisons will be made using the Mann-Whitney U test. Qualitative data will be analyzed using the x2 or Fisher's exact test. Group analysis will be performed at 12, 24, 48, 96 and 144 weeks using the Wilcoxon test. A P value ≤0.05 with a 95% confidence interval will be considered statistically significant.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Men and women ≥18 years of age , diagnosed with HIV, and naive to antiretroviral treatment.
HIV-1 RNA quantified by RT-PCR ≥500 and less than 500,000 copies/mL.
No history of PrEP or PEP use.
Estimated glomerular filtration rate ≥30 mL/min/1.73 m2 SC.
Disqualifiers
Diagnosis of metabolic syndrome.
uncontrolled diabetes
Contraindication to the use of INSTIs.
Known mutations in any of the components of either regimen (second-generation INSTIs, 3TC/FTC, or TAF).
Trial design
Design model
Parallel
Treatments tested in this trial
DTG/3TC
DrugDual therapy of 2 drugs co-formulated in 1 tablet: Dolutegravir 50 mg/ lamivudine 300 mg, it is the experimental group
Bictegravir (BIC) plus Emtricitabine (FTC) plus Tenofovir Alafenamide (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
124 Participants
are divided into 2 treatment groupsGroup A: BIC/TAF/FTCActive comparator 1 intervention
Group B: DTG/3TCExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To determine the effectiveness of Dolutegravir/Lamivudine compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine in ART-naive people with HIV at 144 weeks of treatment.
-Effectiveness: Number of participants with viral load measurement (HIV-1 RNA) \<50 copies/mL at 144 weeks of follow-up for PWH treated with DTG/3TC or BIC/FTC/TAF, expressed in proportions.
Time frame
144 weeks of follow-up with interim analysis at 48 and 96 weeks2
To determine the safety of Dolutegravir/Lamivudine 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 DTG/3TC or BIC/FTC/TAF at 144 weeks, expressed in proportions of new cases.
Time frame
144 weeks, with intermediate measurements at 48 and 96 weeks3
To determine the tolerability of Dolutegravir/Lamivudine compared with Bictegravir/Tenofovir Alafenamide/Emtricitabine in ART-naive people living with HIV at 144 weeks of treatment.
Number of participants with secondary events associated with ART for PWH treated with DTG/3TC or BIC/FTC/TAF at 144 weeks expressed in proportions and percentages, graded from 1 to 4 according to DAIDS: Grade I: mild Grade II: moderate Grade III: severe Grade IV: life-threatening
Time frame
144 weeks, intermediate measurements at 48 and 96 weeksSecondary outcomes
1
Metabolic syndrome incidence in DTG/3TC vs BIC/TAF/FTC at 144 weeks
To determine the incidence of metabolic syndrome in ART-naive PWH initiating a regimen containing DTG/3TC compared with BIC/FTC/TAF after 48 weeks of follow-up, determined by the ATPIII criteria.
Time frame
144 weeks, interim analyses at 48 and 96 weeks2
To evaluate changes in cardiovascular risk based on AHA/ACC score in ART-naive PWH starting a regimen with DTG/3TC compared with BIC/FTC/TAF after 144 weeks of follow-up.
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 DTG/3TC regimen compared with BIC/FTC/TAF after 144 weeks of follow-up. This is classified in percentage as follows: 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, for example: myocardial infarction, stroke, or death due to coronary heart disease or stroke
Time frame
144 weeks, with interim analyses at 48 and 96 weeks3
To determine the incidence of overweight/obesity in ART-naive PWH initiating a DTG/3TC regimen compared with BIC/FTC/TAF after 144 weeks of follow-up.
To determine incidence of overweight/obesity by body mass index (BMI) ART-naive PWH initiating a DTG/3TC regimen compared with BIC/FTC/TAF after 144 weeks of follow-up.
Time frame
144 weeks, with interim analyses at 48 and 96 weeks4
To determine significant weight changes in ART-naive PWH initiating a DTG/3TC regimen compared with BIC/FTC/TAF after 144 weeks of follow-up.
To determine significant weight changes (\>10% body weight gain) in proportions and percentages in ART-naive PWH initiating a DTG/3TC regimen compared with BIC/FTC/TAF after 144 weeks of follow-up.
Time frame
144 weeks, with interim analyses at 48 and 96 weeksSponsors and contacts
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Source ClinicalTrials.gov