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

2019年11月11日 更新者：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.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (実際)

74

段階

  • フェーズ 4

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～99年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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).

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：基礎科学
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
薬：Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

この研究は何を測定していますか？

主要な結果の測定

結果測定
時間枠
Percentage of patients with viral load under 50 copies/mL
時間枠：Week 48
Week 48

二次結果の測定

結果測定
メジャーの説明
時間枠
Percentage of patients without confirmed virological failure.
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
時間枠：Week 48
To evaluate changes in HIV tropism
Week 48
Level of X4 viruses by detected by population sequencing.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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
時間枠：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
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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.
時間枠：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
時間枠：Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of adverse events
時間枠：Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of adverse events
時間枠：Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of adverse events
時間枠：Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of adverse events
時間枠：Week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 48
Cumulative number of grade 3-4 adverse events
時間枠：Week 4
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 4
Cumulative number of grade 3-4 adverse events
時間枠：Week 12
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 12
Cumulative number of grade 3-4 adverse events
時間枠：Week 24
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 24
Cumulative number of grade 3-4 adverse events
時間枠：Week 36
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Week 36
Cumulative number of grade 3-4 adverse events
時間枠：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
時間枠：Up to week 48
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Up to week 48

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

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

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2011年6月1日

一次修了 (実際)

2014年4月1日

研究の完了 (実際)

2014年5月1日

試験登録日

最初に提出

2011年6月17日

QC基準を満たした最初の提出物

2011年6月22日

最初の投稿 (見積もり)

2011年6月23日

学習記録の更新

投稿された最後の更新 (実際)

2019年11月14日

QC基準を満たした最後の更新が送信されました

2019年11月11日

最終確認日

2014年7月1日

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キーワード

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その他の研究ID番号

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