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

11 novembre 2019 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

74

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 99 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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).

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Médicament: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Percentage of patients with viral load under 50 copies/mL
Délai: Week 48
Week 48

Mesures de résultats secondaires

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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 juin 2011

Achèvement primaire (Réel)

1 avril 2014

Achèvement de l'étude (Réel)

1 mai 2014

Dates d'inscription aux études

Première soumission

17 juin 2011

Première soumission répondant aux critères de contrôle qualité

22 juin 2011

Première publication (Estimation)

23 juin 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

14 novembre 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

11 novembre 2019

Dernière vérification

1 juillet 2014

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • PROTEST

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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