Resistance Profile to Antiretroviral Medications in Individuals Living With HIV Who Failed a First-Line Regimen With Tenofovir / Lamivudina and Dolutegravir in Brasil (ARDOL)
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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. The investigators 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:
- 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.
- Determine the genotypic resistance profile among individuals who failed first-line TL+D after 24 weeks of treatment in Brazil.
- 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.
Studietype
Inschrijving (Werkelijk)
Fase
- Niet toepasbaar
Contacten en locaties
Studie Locaties
-
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Amazonas
-
Manaus, Amazonas, Brazilië, 69040-000
- Fundacao De Medicina Tropical Doutor Heitor Vieira Dourado
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Estado de Bahia
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Salvador, Estado de Bahia, Brazilië, 40100-160
- Centro Estadual Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP)
-
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Federal District
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Brasília, Federal District, Brazilië, 70351-580
- Centro Especializado em Doenças Infecciosas (CEDIN-DF)
-
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brazilië, 91350-200
- Hospital Nossa Senhora da Conceicao
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Porto Alegre, Rio Grande do Sul, Brazilië, 90040-000
- LADI - Laboratório de Apoio Diagnóstico em Infectologia (Hospital Universitário Miguel Riet Corrêa Jr)
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Viamão, Rio Grande do Sul, Brazilië, 94480-560
- Serviço Especializado em IST/HIV/AIDS Viamão
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São Paulo
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Guarujá, São Paulo, Brazilië, 11471-000
- Unidade de Infectologia William Rocha
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São Paulo, São Paulo, Brazilië, 08270-070
- Hospital Santa Marcelina
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São Paulo, São Paulo, Brazilië, 04039-032
- Retrovirology Laboratory - UNIFESP
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
Inclusion Criteria:
Age between 18 and 70 ART therapy naive
Exclusion Criteria:
Resistant to reverse transcriptase inhibitor drugs (NRTI)
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Faculteitstoewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: TL+D
TL+D regimen of antiretroviral drugs for 24 weeks
|
Patients will receive the Tenofovir/Lamiduvine NRTI drugs along with the Dolutegravir for 24 weeks.
|
|
Geen tussenkomst: Control
Individuals chosen who have not failed an HIV drug regimen
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Prevalence of TDR
Tijdsspanne: 3 months
|
Comparative analysis of transmitted drug resistance between arms of the study
|
3 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Distribution of subtypes among regions
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 6 months
|
Analysis of CD4+ levels at baseline, week 12 and week 24 in relation to presence of TDR, subtype and region
|
6 months
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Andere studie-ID-nummers
- SPARC-10
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
IPD-tijdsbestek voor delen
IPD-toegangscriteria voor delen
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
- ICF
- ANALYTIC_CODE
- MVO
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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