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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Change of 3rd drug to maraviroc | Experimental | Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Unique | Drug | Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients with viral load under 50 copies/mL | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients without confirmed virological failure. | To evaluate other aspects related to maintanence of virological response. | Up to week 48 |
| Time to loss of virological response (TLOVR) < 200 copies/mL |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Xeral de Vigo | Santiago de Compostela | A Coruña | 15781 | Spain | ||
| Hospital de Elche |
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To evaluate other aspects related to maintanence of virological response.
| Up to week 48 |
| Time to loss of virological response (TLOVR) < 50 copies/mL | 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 | 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 | 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 | 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 | 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 | 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. | To evaluate changes in HIV tropism | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | From baseline to week 48. |
| Median change of HDL cholesterol. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of LDL cholesterol. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of triglycerides | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of AST serum levels. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of ALT serum levels. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of alkaline phosphatase serum levels. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Median change of total bilirubin serum levels. | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | From Baseline to week 48. |
| Cumulative number of adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 4 |
| Cumulative number of adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 12 |
| Cumulative number of adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 24 |
| Cumulative number of adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 36 |
| Cumulative number of adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 48 |
| Cumulative number of grade 3-4 adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 4 |
| Cumulative number of grade 3-4 adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 12 |
| Cumulative number of grade 3-4 adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 24 |
| Cumulative number of grade 3-4 adverse events | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Week 36 |
| Cumulative number of grade 3-4 adverse events | 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 | To evaluate the tolerability and safety with CCR5 antagonist containing regimen | Up to week 48 |
| Elche |
| Alicante |
| 03203 |
| Spain |
| Hospital Son Espases | Palma de Mallorca | Balearic Islands | 07011 | Spain |
| H. U. Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain |
| H. de Bellvitge | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Hospital U. Marqués de Valdecilla | Santander | Cantabria | 39011 | Spain |
| Hospital General de Castellón | Castellon | Castelló | 12004 | Spain |
| Hospital Sta. Lucía/ H. Sta. Mª del Rosell | Cartagena | Murcia | 30203 | Spain |
| Hospital de Cruces | Bilbao | Vizcaya | 48903 | Spain |
| Hospital Gral. U. de Alicante | Alicante | 03010 | Spain |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital de Mataró | Barcelona | 08304 | Spain |
| Hospital Virgen de las Nieves | Granada | 18014 | Spain |
| Hospital U. San Cecilio | Granada | 28012 | Spain |
| Hospital U. Gregorio Marañón | Madrid | 28007 | Spain |
| Hospital Carlos III | Madrid | 28029 | Spain |
| Hospital Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital Clínico San Carlos | Madrid | 28040 | Spain |
| Hospital Reina Sofía de Murcia | Murcia | 30003 | Spain |
| Hospital Sant Pau i Santa Tecla | Tarragona | 43007 | Spain |
| Hospital La Fe | Valencia | 46009 | Spain |
| Hospital Gral. U. de Valencia | Valencia | 46014 | Spain |
| Hospital Arnau de Vilanova | Valencia | 46015 | Spain |
| Hospital U. Dr. Peset | Valencia | 46017 | Spain |