DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV: (PASO-DOBLE)

DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV: an Open-label Randomized Clinical Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Dolutegravir/Lamivudine as a single pill; Drug: Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.

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 investigatora 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
• Enrollment (Estimated): 555
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • H. de Elche
  • Almería, Spain
    • H. de Torrecárdenas
  • Barcelona, Spain
    • H. del Mar
  • Barcelona, Spain, 08036
    • H. Clinic
  • Barcelona, Spain
    • H. de Bellvitge
  • Barcelona, Spain
    • H. de Igualada
  • Barcelona, Spain
    • H. San Joan de Deu
  • Barcelona, Spain
    • H. Sant Creu y Sant Pau
  • Barcelona, Spain
    • H. Vall de Hebron
  • Coruña, Spain
    • CHUAC
  • Guadalajara, Spain, 19002
    • H. Universitario de Guadalajara
  • Huelva, Spain
    • H. Juan Ramón Jimenez
  • Madrid, Spain
    • H. Univ. La Paz
  • Madrid, Spain
    • H. Infanta Leonor
  • Madrid, Spain
    • H. La Princesa
  • Madrid, Spain
    • H. Príncipe de Asturias
  • Madrid, Spain
    • H. Univ. Puerta de Hierro
  • Marbella, Spain
    • H. Costa del Sol
  • Murcia, Spain
    • H. Reina Sofia
  • Oviedo, Spain
    • H. Central de Asturias
  • Palma De Mallorca, Spain
    • H. Son Espases
  • Palma De Mallorca, Spain
    • H. Son Llàtzer
  • Sevilla, Spain
    • H. de Valme
  • Tarragona, Spain
    • H. Joan XXIII
  • Valencia, Spain
    • H. Clínico Univ. de Valencia
  • Valladolid, Spain
    • H Clinico Univ. de Valladolid
  • Vigo, Spain
    • H. Alvaro Cunquerio
  • Zaragoza, Spain
    • H. Clinico Univ. Lozano Bleza
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Hospital Fundación Alcorcón

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 controlled diabetes mellitus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dovato arm; DTG/3TC	Drug: 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.
Active Comparator: Biktarvy arm; BIC/FTC/TAF	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL	Week 48

Secondary Outcome Measures

Outcome Measure	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		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

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA
• Collaborators: ViiV Healthcare
• Investigators: Principal Investigator: Esteban Martinez, MD, H. Clinc de Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Lamivudine; Dolutegravir
• Other Study ID Numbers: GESIDA11720

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No