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

11. november 2019 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

74

Fase

  • Fase 4

Kontakter og lokationer

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

Studiesteder

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

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

18 år til 99 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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).

Studieplan

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

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Medicin: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Percentage of patients with viral load under 50 copies/mL
Tidsramme: Week 48
Week 48

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Percentage of patients without confirmed virological failure.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
Tidsramme: Week 48
To evaluate changes in HIV tropism
Week 48
Level of X4 viruses by detected by population sequencing.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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
Tidsramme: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of adverse events
Tidsramme: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of adverse events
Tidsramme: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of adverse events
Tidsramme: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of adverse events
Tidsramme: Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Cumulative number of grade 3-4 adverse events
Tidsramme: Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of grade 3-4 adverse events
Tidsramme: Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of grade 3-4 adverse events
Tidsramme: Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of grade 3-4 adverse events
Tidsramme: Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of grade 3-4 adverse events
Tidsramme: 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
Tidsramme: Up to week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Up to week 48

Samarbejdspartnere og efterforskere

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

Sponsor

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

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

1. juni 2011

Primær færdiggørelse (Faktiske)

1. april 2014

Studieafslutning (Faktiske)

1. maj 2014

Datoer for studieregistrering

Først indsendt

17. juni 2011

Først indsendt, der opfyldte QC-kriterier

22. juni 2011

Først opslået (Skøn)

23. juni 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

14. november 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

11. november 2019

Sidst verificeret

1. juli 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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