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Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia

11 de novembro de 2019 atualizado por: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia

CCR5 antagonists might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity. The assessment of HIV-1 tropism in proviral DNA could be helpful to inform in which of these subjects CCR5 antagonists could be efficacious.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

The assessment of HIV-1 tropism is needed before starting treatment with a CCR5-antagonist. Several phenotypic and genotyping tropism tests have been developed in the recent years. Phenotypic assays (i.e. TrofileTM and ES-TrofileTM) have been used.in most clinical trials. Genotypic tropism testing, however, is easier, cheaper and faster than phenotypic methods, and can be performed in a local HIV laboratories.

Viral RNA amplification is difficult in subjects with HIV-1 RNA levels <500-1000 copies/mL. In these cases, the optimal source of genetic material is peripheral blood mononuclear cell (PBMC)-associated proviral DNA. Whereas genotypic tropism testing in proviral DNA is technically feasible, it has not been validated as a tool to predict sustained virological response to CCR5-antagonist therapy in subjects with undetectable viremia.

As of today, maraviroc is the only CCR5-antagonist approved for HIV treatment. It has few drug interactions and a good security profile, particularly in terms of lipid and glucose metabolism. Therefore, it might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity or metabolic problems.

This study will evaluate 48-week virological outcomes in aviremic subjects with an R5 virus by proviral genotypic tropism testing who switch the "third drug" of their regimen to maraviroc.

Tipo de estudo

Intervencional

Inscrição (Real)

74

Estágio

  • Fase 4

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Espanha
      • Alicante, Espanha, 03010
        • Hospital Gral. U. de Alicante
      • Barcelona, Espanha, 08035
        • Hospital Vall d'Hebrón
      • Barcelona, Espanha, 08304
        • Hospital de Mataró
      • Granada, Espanha, 18014
        • Hospital Virgen de las Nieves
      • Granada, Espanha, 28012
        • Hospital U. San Cecilio
      • Madrid, Espanha, 28040
        • Hospital Clinico San Carlos
      • Madrid, Espanha, 28007
        • Hospital U. Gregorio Marañón
      • Madrid, Espanha, 28034
        • Hospital Ramón Y Cajal
      • Madrid, Espanha, 28029
        • Hospital Carlos III
      • Murcia, Espanha, 30003
        • Hospital Reina Sofía de Murcia
      • Tarragona, Espanha, 43007
        • Hospital Sant Pau i Santa Tecla
      • Valencia, Espanha, 46015
        • Hospital Arnau de Vilanova
      • Valencia, Espanha, 46009
        • Hospital La Fe
      • Valencia, Espanha, 46014
        • Hospital Gral. U. de Valencia
      • Valencia, Espanha, 46017
        • Hospital U. Dr. Peset
    • A Coruña
      • Santiago de Compostela, A Coruña, Espanha, 15781
        • Hospital Xeral de Vigo
    • Alicante
      • Elche, Alicante, Espanha, 03203
        • Hospital de Elche
    • Baleares
      • Palma de Mallorca, Baleares, Espanha, 07011
        • Hospital Son Espases
    • Barcelona
      • Badalona, Barcelona, Espanha, 08916
        • H. U. Germans Trias i Pujol
      • Hospitalet de Llobregat, Barcelona, Espanha, 08907
        • H. de Bellvitge
    • Cantabria
      • Santander, Cantabria, Espanha, 39011
        • Hospital U. Marques de Valdecilla
    • Castelló
      • Castelló De La Plana, Castelló, Espanha, 12004
        • Hospital General de Castellon
    • Murcia
      • Cartagena, Murcia, Espanha, 30203
        • Hospital Sta. Lucía/ H. Sta. Mª del Rosell
    • Vizcaya
      • Bilbao, Vizcaya, Espanha, 48903
        • Hospital De Cruces

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 99 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. HIV-1 infected patients.
  2. Age 18 or more.
  3. Antiretroviral treatment containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) plus 1 Non-nucleoside reverse-transcriptase inhibitor (NNRTI) or 1 protease inhibitor (PI) or 1 integrase inhibitor (ININ)
  4. Patients receiving stable antiretroviral treatment for at least 6 months.
  5. Viral load under 50 copies/mL in the last 6 months
  6. Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method.
  7. A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria.
  8. An antiretroviral regimen containing a CCR5-antagonist is suitable for the patient (physician criteria).
  9. Voluntary written informed consent.

Exclusion Criteria:

  1. Pregnancy or breast-feeding.
  2. Patient previously treated with maraviroc.
  3. Patients with documented resistance to maraviroc or any other drug considered for the new ARV regimen.
  4. Viral failure in the moment of inclusion.
  5. Bad adherence history or anticipated (investigator criteria).

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Ciência básica
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Medicamento: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
Percentage of patients with viral load under 50 copies/mL
Prazo: Week 48
Week 48

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Percentage of patients without confirmed virological failure.
Prazo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Time to loss of virological response (TLOVR) < 200 copies/mL
Prazo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Time to loss of virological response (TLOVR) < 50 copies/mL
Prazo: Up to week 48
To evaluate other aspects related to maintanence of virological response.
Up to week 48
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Prazo: Week 12
To evaluate other aspects related to maintanence of virological response
Week 12
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Prazo: Week 24
To evaluate other aspects related to maintanence of virological response
Week 24
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Prazo: Week 36
To evaluate other aspects related to maintanence of virological response
Week 36
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Prazo: Week 48
To evaluate other aspects related to maintanence of virological response.
Week 48
Time to treatment discontinuation, overall, and due to factors other than loss of virological response
Prazo: Up to week 48
To evaluate other aspects related to maintanence of virological response
Up to week 48
Association between pre-treatment level of X4 viruses detected by deep sequencing at screening and virological response to maraviroc based therapy at week 48.
Prazo: Week 48
To evaluate changes in HIV tropism
Week 48
Level of X4 viruses by detected by population sequencing.
Prazo: Screening (up to 48 weeks)
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Screening (up to 48 weeks)
Level of X4 viruses by detected by population sequencing.
Prazo: Week 12
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 12
Level of X4 viruses by detected by population sequencing.
Prazo: Week 48
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 48
Level of X4 viruses by detected by deep sequencing.
Prazo: Screening (up to 48 weeks)
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Screening (up to 48 weeks)
Level of X4 viruses by detected by deep sequencing.
Prazo: Week 12
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 12
Level of X4 viruses by detected by deep sequencing.
Prazo: Week 48
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Week 48
High-resolution assessment of virus diversity and X4 level using deep sequencing
Prazo: Week 12
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
Week 12
High-resolution assessment of virus diversity and X4 level using deep sequencing
Prazo: In case of virological failure (week 12 up to virological failure)
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
In case of virological failure (week 12 up to virological failure)
Median change of total cholesterol.
Prazo: From baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From baseline to week 48.
Median change of HDL cholesterol.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of LDL cholesterol.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of triglycerides
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of AST serum levels.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of ALT serum levels.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of alkaline phosphatase serum levels.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Median change of total bilirubin serum levels.
Prazo: From Baseline to week 48.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
From Baseline to week 48.
Cumulative number of adverse events
Prazo: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of adverse events
Prazo: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of adverse events
Prazo: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of adverse events
Prazo: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of adverse events
Prazo: Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Cumulative number of grade 3-4 adverse events
Prazo: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of grade 3-4 adverse events
Prazo: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of grade 3-4 adverse events
Prazo: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of grade 3-4 adverse events
Prazo: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of grade 3-4 adverse events
Prazo: Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Proportion of patients withdrawn from the study and reason for study withdrawal
Prazo: Up to week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Up to week 48

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de junho de 2011

Conclusão Primária (Real)

1 de abril de 2014

Conclusão do estudo (Real)

1 de maio de 2014

Datas de inscrição no estudo

Enviado pela primeira vez

17 de junho de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

22 de junho de 2011

Primeira postagem (Estimativa)

23 de junho de 2011

Atualizações de registro de estudo

Última Atualização Postada (Real)

14 de novembro de 2019

Última atualização enviada que atendeu aos critérios de controle de qualidade

11 de novembro de 2019

Última verificação

1 de julho de 2014

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • PROTEST

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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