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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
74
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
Hospital Xeral de Vigo
Santiago de Compostela, A Coruña, Spain
Percentage of patients with viral load under 50 copies/mL
Time frame: Week 48
Percentage of patients without confirmed virological failure.
To evaluate other aspects related to maintanence of virological response.
Time frame: Up to week 48
Time to loss of virological response (TLOVR) < 200 copies/mL
To evaluate other aspects related to maintanence of virological response.
Time frame: Up to week 48
Time to loss of virological response (TLOVR) < 50 copies/mL
To evaluate other aspects related to maintanence of virological response.
Time frame: Up to week 48
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
To evaluate other aspects related to maintanence of virological response
Time frame: Week 12
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
To evaluate other aspects related to maintanence of virological response
Time frame: Week 24
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
To evaluate other aspects related to maintanence of virological response
Time frame: Week 36
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
To evaluate other aspects related to maintanence of virological response.
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Hospital de Elche
Elche, Alicante, Spain
Hospital Son Espases
Palma de Mallorca, Balearic Islands, Spain
H. U. Germans Trias i Pujol
Badalona, Barcelona, Spain
H. de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital U. Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital General de Castellón
Castellon, Castelló, Spain
Hospital Sta. Lucía/ H. Sta. Mª del Rosell
Cartagena, Murcia, Spain
Hospital de Cruces
Bilbao, Vizcaya, Spain
Hospital Gral. U. de Alicante
Alicante, Spain
...and 14 more locations
Time frame: Week 48
Time to treatment discontinuation, overall, and due to factors other than loss of virological response
To evaluate other aspects related to maintanence of virological response
Time frame: 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.
To evaluate changes in HIV tropism
Time frame: Week 48
Level of X4 viruses by detected by population sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Screening (up to 48 weeks)
Level of X4 viruses by detected by population sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Week 12
Level of X4 viruses by detected by population sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Week 48
Level of X4 viruses by detected by deep sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Screening (up to 48 weeks)
Level of X4 viruses by detected by deep sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Week 12
Level of X4 viruses by detected by deep sequencing.
Evolution of viral tropism in PBMC-associated DNA by population and deep sequencing between screening and week 48 in subjects treated with maraviroc.
Time frame: Week 48
High-resolution assessment of virus diversity and X4 level using deep sequencing
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
Time frame: Week 12
High-resolution assessment of virus diversity and X4 level using deep sequencing
High-resolution assessment of virus diversity and X4 level using deep sequencing at week 12 and at the time of virological failure.
Time frame: In case of virological failure (week 12 up to virological failure)
Median change of total cholesterol.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From baseline to week 48.
Median change of HDL cholesterol.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of LDL cholesterol.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of triglycerides
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of AST serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of ALT serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of alkaline phosphatase serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Median change of total bilirubin serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: From Baseline to week 48.
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 4
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 12
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 24
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 36
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 48
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 4
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 12
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 24
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 36
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Week 48
Proportion of patients withdrawn from the study and reason for study withdrawal
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time frame: Up to week 48