The hypothesize that DTG/3TC will be non-inferior to BIC/FTC/TAF with a 4% margin in virologically suppressed HIV-infected patients. The study will allow claiming for Superiority. Assuming that both DTG and BIC may lead to similar weight gains (approximately 1 kg after 48 weeks) in virologically suppressed HIV-infected patients and that TAF may induce a further weight gain (approximately 1 kg after 48 weeks), also hypothesize that switching to BIC/FTC/TAF may lead to greater weight gain than switching to DTG/3TC over 48 weeks. This trial is a Phase IV, open-label, randomized multicentre clinical trial evaluating the efficacy of DTG/3TC versus BIC/FTC/TAF for the maintenance of virological suppression in HIV patients.
Participants will be randomly assigned in a 1:1 ratio to receive DTG/3TC or BIC/FTC/TAF. Randomization will be stratified by sex and TAF use at baseline. At least 33% of the patients included will be women. The investigator will also endeavour to recruit as many non-Caucasian participants as possible. Patients with TAF-containing regimens at baseline will be limited to 25% or less of the total number of participants. Three sub-studies will be performed: Omics sub-study ; Senescence sub-study; Fat biopsies sub-study. Omics sub-study: Assess the mechanistic pathways involved on weight changes associated with switching to BIC/FTC/TAF vs. DTG/3TC. Senescence sub-study: Assess the potential effects on the telomere length, epigenetic age and oxidative stress markers of switching to BIC/FTC/TAF vs. DTG/3TC. Fat biopsies sub-study: To assess potential effects of switching to BIC/FTC/TAF vs. DTG/3TC on expression of marker genes of mitochondrial function, adipogenesis, and inflammation in subcutaneous fat tissue. Assays on adipose tissue gene expression will be complemented by analysis in serum of adipokines representative of adipose tissue function (leptin, adiponectin), and inflammation biomarkers (TNFalpha, MCP-1, IL-6, IL-8, IL-10, IL-18).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
554
\- Dose: Dolutegravir 50mg/ Lamivudine 300 mg -Route of adminstration: oral -Schedule of administration: once a day for 96 weeks.
* Dose: Bictegravir 50 mg/Emtricitabine 200 mg /Tenofovir alafenamide 25 mg * Route of adminstration: oral * Schedule of administration: once a day for 96 weeks.
H. Marina Baixa
Villajoyosa, Alicante, Spain
Hospital Fundación Alcorcón
Alcorcón, Madrid, Spain
CHUAC
A Coruña, Spain
H. General Universitario Dr. Balmis
Alicante, Spain
H. de Elche
Alicante, Spain
H. de Torrecárdenas
Almería, Spain
H. Clinic
Barcelona, Spain
H. Germans Trias i Pujol
Barcelona, Spain
H. de Bellvitge
Barcelona, Spain
H. de Igualada
Barcelona, Spain
...and 23 more locations
Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL
Time frame: Week 48
Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL
Time frame: week 96
Proportion of patients with plasma HIV-1 RNA <50 copies/mL
Time frame: Week 48 and week 96
Absolute weight
Time frame: Basal, week 48 y week 96
BMI change
Time frame: Basal, week 48 y week 96
Proportion of patients with weight change >5%
Time frame: Basal, week 48 y week 96
Absolute values in CD4+ cells count
Time frame: Basal, week 48 y week 96
Changes in CD4+ cells count
Time frame: Basal, week 48 y week 96
Absolute values CD4:CD8 ratio
Time frame: Basal, week 48 y week 96
Changes CD4:CD8 ratio
Time frame: Basal, week 48 y week 96
Change in total and regional (trunk and extremities) fat by DXA
Time frame: Basal, week 48 y week 96
Change in total and regional (trunk and extremities) fat-free mass by DXA
Time frame: Basal, week 48 y week 96
Change in lumbar and hip bone mineral density (BMD) by DXA
Time frame: Basal, week 48 y week 96
Change trabecular bone score (TBS) by DXA
Time frame: Basal, week 48 y week 96
Change in subcutaneous and visceral fat (CT)
Time frame: Basal, week 48 y week 96
Change in fasting glucose cholesterol, triglycerides), and FIB-4 score
Time frame: Basal, week 48 y week 96
Change insulin cholesterol, triglycerides), and FIB-4 score
Time frame: Basal, week 48 y week 96
Change in HOMA-IR cholesterol, triglycerides), and FIB-4 score
Time frame: Basal, week 48 y week 96
Change in HbA1c cholesterol, triglycerides), and FIB-4 score
Time frame: Basal, week 48 y week 96
Change in plasma lipids (total, HDL, and LDL) cholesterol, triglycerides), and FIB-4 score
Time frame: Basal, week 48 y week 96
Changes in estimated glomerular filtration rate (CKD-EPI)
Time frame: Basal, week 48 y week 96
Changes in urinary protein/creatinine
Time frame: Basal, week 48 y week 96
Change in blood pressure
Systolic and Diastolic Blood Pressure
Time frame: Basal, week 48 y week 96
Change in sleep quality (Pittsburg Sleep Quality Index)
Pittsburg Sleep Quality Index
Time frame: From basal, until week 96 , in each visit
Change in anxiety and depression (HAD) quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM
Anxiety and depression (HAD) questionnaire
Time frame: From basal, until week 96 , in each visit
Change in quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM)
Quality of life (HIV-SI/SDM) questionnaire
Time frame: From basal, until week 96 , in each visit
Incidence and severity of adverse events (clinical and laboratory)
Time frame: From basal, until week 96 , in each visit
Incidence of adverse events leading to treatment discontinuation.
Time frame: From basal, until week 96 , in each visit
Incidence of genotypic resistance mutations in participants with virological failure
Time frame: Week 48 and week 96
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