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Resistance Profile to Antiretroviral Medications in Individuals Living With HIV Who Failed a First-Line Regimen With Tenofovir / Lamivudina and Dolutegravir in Brasil (ARDOL)

25. maj 2026 opdateret af: Ricardo Sobhie Diaz, Federal University of São Paulo

The goal of this study is to understand the profile of individuals who demonstrate transmitted drug resistance to Dolutegravir (DTG) among PLHIV in Brazil in terms of the subtypes of virus and other individual characteristics after 24 weeks of treatment with a regimen of DTG, Tenofovir, and Lamivudine (TL+D). The study also seeks to determine what alterations occur in the 3'-PPT region of the HIV virus in patients with failing the TL+D regimen.

The test group will be compared to a control group of individuals randomly selected whose viral control remains below detection limit (50 copies/mL) for 24 weeks after the initiation of treatment. The study uses clinics in cities in each of the five regions of Brazil: South region (Porto Alegre, Viamão), Southeast region (São Paulo, Santos, Guarujá), Northeast region (Salvador), Center West region (Brasília), and the North region (Manaus). Porto Alegre and Viamão are of interest because of the strong presence of subtype C in the South region. Salvador is a focus for subtype F of HIV. Finally, in Santos there is a strong presence of recombinant forms of subtypes F and B. These non-B subtypes are important to the study as they are typical of other medium and low income countries.

The plan for the study includes 200 cases who will receive the TL+D medication for 24 weeks (50 in each region) and 400 controls again spread among the regions on a 1 (case): 2(control ratio.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

In November 2018, 170,000 individuals were receiving Dolutegravir through the public health system. It is a public health priority to evaluate the risk of virological failure and the subsequent development of resistance to integrase inhibitors in our setting. It has recently been shown that, in addition to resistance mutations in the integrase region of the pol gene, mutations in the 3'-PPT region (nef gene) also emerge and contribute to decreased susceptibility to Dolutegravir. The objectives of this work are to investigate the influence of transmitted antiretroviral resistance, the profile of HIV subtypes, and immunological and virological characteristics among individuals who failed first-line treatment with Tenofovir/Lamivudine and Dolutegravir (TL+D) after 24 weeks of treatment in Brazil. We also seek to determine the genotypic resistance profile among individuals who failed the first-line TL+D regimen after 24 weeks of treatment in Brazil. To determine what alterations in the 3'-PPT are observed in viruses from patients failing TL+D and to assess if this new resistance pathway contributes to acquired resistance to the drug in clinical practice.

This is a nested case-control prospective study comparing in a 2:1 ratio the baseline HIV-1 genotypic profile of individuals with virological failure on the TL+D regimen after 24 weeks of treatment (cases) to randomly selected individuals with viral control with viral load below the detection limits of 50 copies/mL, 24 weeks after treatment initiation (controls).

HYPOTHESIS: The central hypothesis is that transmitted drug resistance (TDR) may be associated with and contribute to virological failure with dolutegravir (DTG) in clinical practice. To test this central hypothesis, we will identify DTG-containing regimens with failure in people living with HIV in Brazil, a model country for large-scale DTG implementation, where multiple HIV subtypes cocirculate.

PRIMARY RESEARCH OBJECTIVE:

  1. Investigate the influence of transmitted drug resistance, the profile of HIV subtypes, and immunological and virological characteristics among individuals who failed the first-line TL+D regimen after 24 weeks of treatment in Brazil.
  2. Determine the genotypic resistance profile among individuals who failed first-line TL+D after 24 weeks of treatment in Brazil.
  3. Determine what alterations in the 3'-PPT are observed in viruses from patients failing TL+D and assess if this new resistance pathway contributes to acquired drug resistance in clinical practice.

RISK AND BENEFIT ASSESSMENT:

RISKS: The risks associated with this study include discomfort at the needle puncture site for blood draws or the possible appearance of a bruise. Discomfort or occasional bruising occur with the same frequency as any blood draw for exams that a patient is already accustomed to.

BENEFITS: Patients will receive no direct benefit from participation in this study. The resistance tests performed may eventually help in selecting more effective antiretroviral drugs if treatment is not fully effective in controlling the HIV in the body. There will be no financial costs or compensation for participation in this study.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

777

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Brasilien
    • Amazonas
      • Manaus, Amazonas, Brasilien, 69040-000
        • Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brasilien, 40100-160
        • Centro Estadual Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP)
    • Federal District
      • Brasília, Federal District, Brasilien, 70351-580
        • Centro Especializado em Doenças Infecciosas (CEDIN-DF)
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brasilien, 91350-200
        • Hospital Nossa Senhora da Conceição
      • Porto Alegre, Rio Grande do Sul, Brasilien, 90040-000
        • LADI - Laboratório de Apoio Diagnóstico em Infectologia (Hospital Universitário Miguel Riet Corrêa Jr)
      • Viamão, Rio Grande do Sul, Brasilien, 94480-560
        • Serviço Especializado em IST/HIV/AIDS Viamão
    • São Paulo
      • Guarujá, São Paulo, Brasilien, 11471-000
        • Unidade de Infectologia William Rocha
      • São Paulo, São Paulo, Brasilien, 08270-070
        • Hospital Santa Marcelina
      • São Paulo, São Paulo, Brasilien, 04039-032
        • Retrovirology Laboratory - UNIFESP

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria:

Age between 18 and 70 ART therapy naive

Exclusion Criteria:

Resistant to reverse transcriptase inhibitor drugs (NRTI)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Faktoriel opgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: TL+D
TL+D regimen of antiretroviral drugs for 24 weeks
Medicin: TL+D antiretroviral
Patients will receive the Tenofovir/Lamiduvine NRTI drugs along with the Dolutegravir for 24 weeks.
Ingen indgriben: Control
Individuals chosen who have not failed an HIV drug regimen

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Prevalence of TDR
Tidsramme: 3 months
Comparative analysis of transmitted drug resistance between arms of the study
3 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Distribution of subtypes among regions
Tidsramme: 4 months
The distribution of subtypes in the five regions of Brazil in light of existence or not of TDR
4 months
Sequence of 3'-PPT region of NEF
Tidsramme: 6 months
Comparison of the sequence of the 3'-PPT region of the NEF gene related to the existence of TDR, subtype and region
6 months
Viral Load
Tidsramme: 6 months
Descriptive analysis of viral load for cases and controls at baseline, week 12 and week 24, including comparison related to presence of TDR and subtypes
6 months
CD4+ Levels
Tidsramme: 6 months
Analysis of CD4+ levels at baseline, week 12 and week 24 in relation to presence of TDR, subtype and region
6 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Federal University of São Paulo

Samarbejdspartnere

Gilead Sciences

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

13. april 2022

Primær færdiggørelse (Faktiske)

8. marts 2024

Studieafslutning (Faktiske)

8. marts 2024

Datoer for studieregistrering

Først indsendt

25. maj 2026

Først indsendt, der opfyldte QC-kriterier

25. maj 2026

Først opslået (Faktiske)

1. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

1. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. maj 2026

Sidst verificeret

1. oktober 2025

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Andre undersøgelses-id-numre

  • SPARC-10

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

The sponsors plan to divulge all the anonymized data through a publicly available repository at a site to be determined.

IPD-delingstidsramme

The IPD will be available by June 2026 and stay publicly available for 10 years (until May 2036).

IPD-delingsadgangskriterier

Access will be publicly available and include all the data from the project. Access will be by accessing the public repository.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med HIV

Kliniske forsøg med TL+D antiretroviral

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Betingelser

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