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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01378910
First received: June 17, 2011
Last updated: July 2, 2014
Last verified: July 2014

June 17, 2011
July 2, 2014
June 2011
April 2014   (final data collection date for primary outcome measure)
Percentage of patients with viral load under 50 copies/mL [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01378910 on ClinicalTrials.gov Archive Site
  • Percentage of patients without confirmed virological failure. [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response.
  • Time to loss of virological response (TLOVR) < 200 copies/mL [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response.
  • Time to loss of virological response (TLOVR) < 50 copies/mL [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response.
  • Proportion of patients treated with maraviroc with viral load under 50 copies/mL [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response
  • Proportion of patients treated with maraviroc with viral load under 50 copies/mL [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response
  • Proportion of patients treated with maraviroc with viral load under 50 copies/mL [ Time Frame: Week 36 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response
  • Proportion of patients treated with maraviroc with viral load under 50 copies/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response.
  • Time to treatment discontinuation, overall, and due to factors other than loss of virological response [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
    To evaluate other aspects related to maintanence of virological response
  • 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 ] [ Designated as safety issue: No ]
    To evaluate changes in HIV tropism
  • Level of X4 viruses by detected by population sequencing. [ Time Frame: Screening (up to 48 weeks) ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • Level of X4 viruses by detected by population sequencing. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • Level of X4 viruses by detected by population sequencing. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • Level of X4 viruses by detected by deep sequencing. [ Time Frame: Screening (up to 48 weeks) ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • Level of X4 viruses by detected by deep sequencing. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • Level of X4 viruses by detected by deep sequencing. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
  • High-resolution assessment of virus diversity and X4 level using deep sequencing [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
  • 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) ] [ Designated as safety issue: No ]
    High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
  • Median change of total cholesterol. [ Time Frame: From baseline to week 48. ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of HDL cholesterol. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of LDL cholesterol. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of triglycerides [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of AST serum levels. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: No ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of ALT serum levels. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: No ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of alkaline phosphatase serum levels. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: No ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Median change of total bilirubin serum levels. [ Time Frame: From Baseline to week 48. ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of adverse events [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of adverse events [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of adverse events [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of adverse events [ Time Frame: Week 36 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of adverse events [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of grade 3-4 adverse events [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of grade 3-4 adverse events [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of grade 3-4 adverse events [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of grade 3-4 adverse events [ Time Frame: Week 36 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Cumulative number of grade 3-4 adverse events [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
  • Proportion of patients withdrawn from the study and reason for study withdrawal [ Time Frame: Up to week 48 ] [ Designated as safety issue: Yes ]
    To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Same as current
Not Provided
Not Provided
 
Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
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.

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.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
HIV
Drug: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Experimental: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Intervention: Drug: Unique
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
74
May 2014
April 2014   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01378910
PROTEST
No
Fundacio Lluita Contra la SIDA
Fundacio Lluita Contra la SIDA
Not Provided
Not Provided
Fundacio Lluita Contra la SIDA
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP