Efficacy of Dolutegravir Plus Lamivudine in HIV-1-infected Treatment-naïve Adults Without a Baseline Genotyping Test

NCT04549467 | Completed Phase 4 DMC

• 1 other identifier: IDEAA 002
• Study Type: interventional
• Target: 244
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of DTG + 3TC versus DTG + TDF/FTC over 48 weeks in HIV-1 naive patients in a real life setting with no baseline HIV genotypic resistance testing available.

Conditions

Hiv; HIV-1-infection

Keywords

hiv; antiretroviral treatment; dolutegravir; dual therapy

Outcome Measures

Primary Outcomes (1)

• Virologic Efficacy

  To demonstrate the non-inferior antiviral activity (VL \< 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV-1 naïve adult patients without baseline genotypic resistance testing available. Endpoint: Proportion of subjects with plasma HIV-1 RNA \<50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm \[Missing, Switch or Discontinuation = Failure (MSD=F)\] for the intent-to-treat exposed (ITT-E) population.

  48 weeks

Secondary Outcomes (2)

• Genetic barrier

  48 weeks

• Efficacy in presence of any major resistanceassociated mutation al baseline

  48 weeks

Study Arms (2)

Dolutegravir + lamivudine

EXPERIMENTAL

Dolutegravir 50 mg, 1 tablet QD plus lamivudine 300 mg, 1 tablet QD

Drug: Lamivudine 300 MG

Dolutegravir + emtricitabine/tenofovir (FTC/TDF)

ACTIVE COMPARATOR

Dolutegravir 50 mg, 1 tablet QD plus FTC/TDF 200/300 mg, 1 coformulated tablet QD

Drug: Emtricitabine / Tenofovir Disoproxil Pill

Interventions

Lamivudine 300 MG DRUG

Experimental arm

Also known as: 3TC, dolutegravir

Dolutegravir + lamivudine

Emtricitabine / Tenofovir Disoproxil Pill DRUG

Active Comparator

Also known as: truvada, dolutegravir

Dolutegravir + emtricitabine/tenofovir (FTC/TDF)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject should be antiretroviral naïve (defined as \<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection).
• Age ≥ 18 years
• Screening plasma HIV-1 RNA ≥1000 c/mL
• CD4 cell count nadir: any value
• Effective contraception for women of childbearing potential.
• Informed consent form signed by patient and investigator

You may not qualify if:

• History of suicide ideation, intention or action.
• Evidence of HBV infection based on the results of testing at Screening\* for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (antiHBs or HBsAb), and HBV DNA as follows: Subjects positive for HBsAg are excluded; Subjects negative for anti-HBs and HBsAg but positive for anti-HBc and positive for HBV DNA are excluded.
• Anticipated need for any HCV therapy during the first 48 weeks of the study.
• Acute symptomatic HIV Infection.
• Any active Opportunistic Infection (category C, CDC 2014).
• Current pregnancy or breastfeeding.
• No effective contraception for the women of childbearing.
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
• ALT (Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia).
• Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice).
• Creatinine clearance of \<50 mL/min/1.73 m2 (Cockroft-Gault method).
• History or presence of allergy to the trial drugs or their components.
• Severe hepatic insufficiency (Child Pugh Class C).
• Any available historical resistance test result.

Sponsors & Collaborators

• Fundacion IDEAA: lead
• ViiV Healthcare: collaborator

Study Sites (1)

Fundacion IDEAA

Buenos Aires, 1405, Argentina

Location

Related Publications (1)

• Cordova E, Hernandez Rendon J, Mingrone V, Martin P, Arevalo Calderon G, Seleme S, Ballivian J, Porteiro N. Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial. Lancet HIV. 2025 Feb;12(2):e95-e104. doi: 10.1016/S2352-3018(24)00294-7. Epub 2025 Jan 15.

  PMID: 39826566 DERIVED

Related Links

• Fundacion IDEAA web page

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Lamivudine; dolutegravir; Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Ezequiel Cordova, MD

  Fundacion IDEAA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: November 17, 2020
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

AR (1)