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Completed

NCT Number: NCT01378910

Genotypic 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.

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Key information

Conditions

HIV

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital Xeral de Vigo, Santiago de Compostela, A Coruña, Spain

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • HIV-1 infected patients.
  • Age 18 or more.
  • 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)
  • Patients receiving stable antiretroviral treatment for at least 6 months.
  • Viral load under 50 copies/mL in the last 6 months
  • Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method.
  • A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria.
  • An antiretroviral regimen containing a CCR5-antagonist is suitable for the patient (physician criteria).
  • Voluntary written informed consent.

Exclusion criteria

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

Treatment and study plan

Unique

Drug

Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)

Primary outcomes

  1. Percentage of patients with viral load under 50 copies/mL

    Time frame: Week 48

Secondary outcomes

  1. Percentage of patients without confirmed virological failure.

    Time frame: Up to week 48

    To evaluate other aspects related to maintanence of virological response.

  2. Time to loss of virological response (TLOVR) < 200 copies/mL

    Time frame: Up to week 48

    To evaluate other aspects related to maintanence of virological response.

  3. Time to loss of virological response (TLOVR) < 50 copies/mL

    Time frame: Up to week 48

    To evaluate other aspects related to maintanence of virological response.

  4. Proportion of patients treated with maraviroc with viral load under 50 copies/mL

    Time frame: Week 12

    To evaluate other aspects related to maintanence of virological response

  5. Proportion of patients treated with maraviroc with viral load under 50 copies/mL

    Time frame: Week 24

    To evaluate other aspects related to maintanence of virological response

  6. Proportion of patients treated with maraviroc with viral load under 50 copies/mL

    Time frame: Week 36

    To evaluate other aspects related to maintanence of virological response

  7. Proportion of patients treated with maraviroc with viral load under 50 copies/mL

    Time frame: Week 48

    To evaluate other aspects related to maintanence of virological response.

  8. Time to treatment discontinuation, overall, and due to factors other than loss of virological response

    Time frame: Up to week 48

    To evaluate other aspects related to maintanence of virological response

  9. Association between pre-treatment level of X4 viruses detected by deep sequencing at screening and virological response to maraviroc based therapy at week 48.

    Time frame: Week 48

    To evaluate changes in HIV tropism

  10. Level of X4 viruses by detected by population sequencing.

    Time frame: 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.

  11. Level of X4 viruses by detected by population sequencing.

    Time frame: 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.

  12. Level of X4 viruses by detected by population sequencing.

    Time frame: 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.

  13. Level of X4 viruses by detected by deep sequencing.

    Time frame: 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.

  14. Level of X4 viruses by detected by deep sequencing.

    Time frame: 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.

  15. Level of X4 viruses by detected by deep sequencing.

    Time frame: 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.

  16. High-resolution assessment of virus diversity and X4 level using deep sequencing

    Time frame: Week 12

    High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.

  17. High-resolution assessment of virus diversity and X4 level using deep sequencing

    Time frame: 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.

  18. Median change of total cholesterol.

    Time frame: From baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  19. Median change of HDL cholesterol.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  20. Median change of LDL cholesterol.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  21. Median change of triglycerides

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  22. Median change of AST serum levels.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  23. Median change of ALT serum levels.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  24. Median change of alkaline phosphatase serum levels.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  25. Median change of total bilirubin serum levels.

    Time frame: From Baseline to week 48.

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  26. Cumulative number of adverse events

    Time frame: Week 4

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  27. Cumulative number of adverse events

    Time frame: Week 12

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  28. Cumulative number of adverse events

    Time frame: Week 24

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  29. Cumulative number of adverse events

    Time frame: Week 36

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  30. Cumulative number of adverse events

    Time frame: Week 48

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  31. Cumulative number of grade 3-4 adverse events

    Time frame: Week 4

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  32. Cumulative number of grade 3-4 adverse events

    Time frame: Week 12

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  33. Cumulative number of grade 3-4 adverse events

    Time frame: Week 24

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  34. Cumulative number of grade 3-4 adverse events

    Time frame: Week 36

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  35. Cumulative number of grade 3-4 adverse events

    Time frame: Week 48

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

  36. Proportion of patients withdrawn from the study and reason for study withdrawal

    Time frame: Up to week 48

    To evaluate the tolerability and safety with CCR5 antagonist containing regimen

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
Jun 23, 2011
Registry last updated
Nov 14, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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