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

Fundacion SEIMC-GESIDA

Status and phase: Completed; Phase 4

Conditions: HIV-1-infection

Treatments: Drug: Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.; Drug: Dolutegravir/Lamivudine as a single pill

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04884139

GESIDA11720

Details and patient eligibility

About

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.

Full 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).

Enrollment: 554 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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554 participants in 2 patient groups

Dovato arm

Experimental group

Description:

DTG/3TC

Treatment:

Drug: Dolutegravir/Lamivudine as a single pill

Biktarvy arm

Active Comparator group

Description:

BIC/FTC/TAF

Treatment:

Drug: Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.