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

• Percentage of patients with viral load under 50 copies/mL [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
  

• 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
  
  

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.