DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV:

NCT ID: NCT04884139

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 554 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-14
• Study Completion Date: 2025-03-13

Brief Summary

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.

Detailed Description

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).

Conditions

HIV-1-infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dovato arm

DTG/3TC

Group Type: EXPERIMENTAL

Dolutegravir/Lamivudine as a single pill

Intervention Type: DRUG

\- Dose: Dolutegravir 50mg/ Lamivudine 300 mg -Route of adminstration: oral -Schedule of administration: once a day for 96 weeks.

Biktarvy arm

BIC/FTC/TAF

Group Type: ACTIVE_COMPARATOR

Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.

Intervention Type: DRUG

• Dose: Bictegravir 50 mg/Emtricitabine 200 mg /Tenofovir alafenamide 25 mg
• Route of adminstration: oral
• Schedule of administration: once a day for 96 weeks.

Interventions

Dolutegravir/Lamivudine as a single pill

\- Dose: Dolutegravir 50mg/ Lamivudine 300 mg -Route of adminstration: oral -Schedule of administration: once a day for 96 weeks.

Intervention Type: DRUG

Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.

• Dose: Bictegravir 50 mg/Emtricitabine 200 mg /Tenofovir alafenamide 25 mg
• Route of adminstration: oral
• Schedule of administration: once a day for 96 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Understanding the study information provided and being capable of giving written informed consent.

2. Confirmed HIV infection.

3. ≥18 years of age on the day of screening.

4. HIV RNA <50 copies/mL for at least 24 weeks before screening.

5. Receiving any regimen for HIV containing more than 1 pill a day or any single tablet regimen containing at least one of the following: cobicistat-boosting, efavirenz, or tenofovir disoproxyl fumarate, for at least 24 weeks before screeningPatients with TAF are expected from cobiscitat-boosting single tablet regimens containing darunavir or elvitegravir and from more-than-1-pill-a-day regimens containing TAF/FTC; their participation will be limited to ≤25%. Patients will be stratified according to the presence or not of TAF in their regimens.

6. No evidence of previous viral failure.

7. No known or suspected resistance to study drugs.

8. Females of childbearing potential, must be using highly effective methods of contraception from study inclusion and for at least 4 weeks after last study visit; all female volunteers must be willing to undergo urine pregnancy testing at the time points specified in the schedules of events.

9. Clinical stability: Participants who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.

Exclusion Criteria

1. Is pregnant or lactating at the screening visit or at any time during the study or is planning on becoming pregnant over the duration of the study.

2. Evidence of Hepatitis B virus infection based on at least one positive result of testing at Screening for Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti- HBc).

3. Previous or current therapy with dolutegravir or bictegravir.

4. History of allergy to study drugs or their components.

5. Liver disease as defined by ALT >= 5x ULN or ALT >=3xULN and Bili =1.5xULN (with >35% direct bilirubin).

6. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones);

7. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification and/or anticipated need for Hep C treatment.

8. Kidney disease as defined by CKD-EPI <50ml/min.

9. Any recently (<=6 months) diagnosed clinical condition or recently (<=6 months) initiated concomitant therapy (see Section 6.5) that may primarily affect weight or body composition. E.g., including but not limited to endocrine disorders, osteoporosis or medications to treat these clinical conditions, with the exception of ontrolled diabetes mellitus.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

Fundacion SEIMC-GESIDA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esteban Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

H. Clinc de Barcelona

Locations

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

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, , Spain

H. Juan Ramón Jimenez

Huelva, , Spain

Hospital Universitari Arnau de Vilanova

Lleida, , 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

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 40489982 (View on PubMed)

Other Identifiers

GESIDA11720

Identifier Type: -

Identifier Source: org_study_id