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| Name | Class |
|---|---|
| ViiV Healthcare | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dovato arm | Experimental | DTG/3TC |
|
| Biktarvy arm | Active Comparator | BIC/FTC/TAF |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dolutegravir/Lamivudine as a single pill | Drug | - Dose: Dolutegravir 50mg/ Lamivudine 300 mg -Route of adminstration: oral -Schedule of administration: once a day for 96 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL | week 96 | |
| Proportion of patients with plasma HIV-1 RNA <50 copies/mL | Week 48 and week 96 | |
| Absolute weight |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Esteban Martinez, MD | H. Clinc de Barcelona | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Marina Baixa | Villajoyosa | Alicante | 03570 | Spain | ||
| Hospital Fundación Alcorcón |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40489982 | Derived | Ryan P, Blanco JL, Masia M, Garcia-Fraile L, Crusells MJ, Domingo P, Curran A, Guerri-Fernandez R, Bernal E, Bravo J, Revollo B, Macias J, Tiraboschi JM, Montejano R, Amador C, Torralba M, Merino D, Diaz-Brito V, Galindo MJ, Ferra S, Villoslada A, Losa JE, Fanjul FJ, Perez-Stachowski X, Peraire J, Portilla J, de la Fuente S, Duenas C, Vazquez MJ, Di Gregorio S, Esteban H, Gil P, de Miguel M, Alejos B, Martinez E; PASO-DOBLE study group. Maintenance therapy with dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide in people with HIV (PASO-DOBLE): 48-week results from a randomised, multicentre, open-label, non-inferiority trial. Lancet HIV. 2025 Jul;12(7):e473-e484. doi: 10.1016/S2352-3018(25)00105-5. Epub 2025 Jun 7. |
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| Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill. | Drug |
|
|
| Basal, week 48 y week 96 |
| BMI change | Basal, week 48 y week 96 |
| Proportion of patients with weight change >5% | Basal, week 48 y week 96 |
| Absolute values in CD4+ cells count | Basal, week 48 y week 96 |
| Changes in CD4+ cells count | Basal, week 48 y week 96 |
| Absolute values CD4:CD8 ratio | Basal, week 48 y week 96 |
| Changes CD4:CD8 ratio | Basal, week 48 y week 96 |
| Change in total and regional (trunk and extremities) fat by DXA | Basal, week 48 y week 96 |
| Change in total and regional (trunk and extremities) fat-free mass by DXA | Basal, week 48 y week 96 |
| Change in lumbar and hip bone mineral density (BMD) by DXA | Basal, week 48 y week 96 |
| Change trabecular bone score (TBS) by DXA | Basal, week 48 y week 96 |
| Change in subcutaneous and visceral fat (CT) | Basal, week 48 y week 96 |
| Change in fasting glucose cholesterol, triglycerides), and FIB-4 score | Basal, week 48 y week 96 |
| Change insulin cholesterol, triglycerides), and FIB-4 score | Basal, week 48 y week 96 |
| Change in HOMA-IR cholesterol, triglycerides), and FIB-4 score | Basal, week 48 y week 96 |
| Change in HbA1c cholesterol, triglycerides), and FIB-4 score | Basal, week 48 y week 96 |
| Change in plasma lipids (total, HDL, and LDL) cholesterol, triglycerides), and FIB-4 score | Basal, week 48 y week 96 |
| Changes in estimated glomerular filtration rate (CKD-EPI) | Basal, week 48 y week 96 |
| Changes in urinary protein/creatinine | Basal, week 48 y week 96 |
| Change in blood pressure | Systolic and Diastolic Blood Pressure | Basal, week 48 y week 96 |
| Change in sleep quality (Pittsburg Sleep Quality Index) | Pittsburg Sleep Quality Index | 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 | 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 | From basal, until week 96 , in each visit |
| Incidence and severity of adverse events (clinical and laboratory) | From basal, until week 96 , in each visit |
| Incidence of adverse events leading to treatment discontinuation. | From basal, until week 96 , in each visit |
| Incidence of genotypic resistance mutations in participants with virological failure | Week 48 and week 96 |
| Alcorcón |
| Madrid |
| 28922 |
| Spain |
| CHUAC | A Coruña | Spain |
| H. General Universitario Dr. Balmis | Alicante | 03010 | Spain |
| H. de Elche | Alicante | Spain |
| H. de Torrecárdenas | Almería | Spain |
| H. Clinic | Barcelona | 08036 | Spain |
| H. Germans Trias i Pujol | Barcelona | 08916 | Spain |
| H. de Bellvitge | Barcelona | Spain |
| H. de Igualada | Barcelona | Spain |
| H. del Mar | Barcelona | Spain |
| H. San Joan de Deu | Barcelona | Spain |
| H. Sant Creu y Sant Pau | Barcelona | Spain |
| H. Vall de Hebron | Barcelona | Spain |
| H. Universitario de Guadalajara | Guadalajara | 19002 | Spain |
| H. Juan Ramón Jimenez | Huelva | Spain |
| Hospital Universitari Arnau de Vilanova | Lleida | 25198 | Spain |
| H. Infanta Leonor | Madrid | Spain |
| H. La Princesa | Madrid | Spain |
| H. Príncipe de Asturias | Madrid | Spain |
| H. Univ. La Paz | Madrid | Spain |
| H. Univ. Puerta de Hierro | Madrid | Spain |
| H. Costa del Sol | Marbella | Spain |
| H. Reina Sofía | Murcia | Spain |
| H. Central de Asturias | Oviedo | Spain |
| H. Son Espases | Palma de Mallorca | Spain |
| H. Son Llatzer | Palma de Mallorca | Spain |
| H. de Valme | Seville | Spain |
| H. Joan XXIII | Tarragona | Spain |
| H. Clínico Univ. de Valencia | Valencia | Spain |
| H Clinico Univ. de Valladolid | Valladolid | Spain |
| H. Alvaro Cunquerio | Vigo | Spain |
| H. Clinico Univ. Lozano Bleza | Zaragoza | Spain |
| ID | Term |
|---|---|
| C562325 | dolutegravir |
| D019259 | Lamivudine |
| C000620396 | bictegravir |
| ID | Term |
|---|---|
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D015224 | Dideoxynucleosides |
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