Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
- Conditions
- HIV
- Interventions
- Drug: Unique
- Registration Number
- NCT01378910
- Lead Sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Change of 3rd drug to maraviroc Unique Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
- Primary Outcome Measures
Name Time Method Percentage of patients with viral load under 50 copies/mL Week 48
- Secondary Outcome Measures
Name Time Method Percentage of patients without confirmed virological failure. Up to week 48 To evaluate other aspects related to maintanence of virological response.
Time to loss of virological response (TLOVR) < 200 copies/mL Up to week 48 To evaluate other aspects related to maintanence of virological response.
Time to loss of virological response (TLOVR) < 50 copies/mL Up to week 48 To evaluate other aspects related to maintanence of virological response.
Proportion of patients treated with maraviroc with viral load under 50 copies/mL Week 48 To evaluate other aspects related to maintanence of virological response.
Level of X4 viruses by detected by population sequencing. 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.
Level of X4 viruses by detected by deep sequencing. 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.
High-resolution assessment of virus diversity and X4 level using deep sequencing 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.
Median change of total cholesterol. From baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of HDL cholesterol. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of LDL cholesterol. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Time to treatment discontinuation, overall, and due to factors other than loss of virological response Up to week 48 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. Week 48 To evaluate changes in HIV tropism
Median change of triglycerides From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of AST serum levels. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of ALT serum levels. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of alkaline phosphatase serum levels. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Median change of total bilirubin serum levels. From Baseline to week 48. To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Cumulative number of adverse events Week 48 To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Cumulative number of grade 3-4 adverse events Week 48 To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Proportion of patients withdrawn from the study and reason for study withdrawal Up to week 48 To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Trial Locations
- Locations (24)
Hospital Carlos III
🇪🇸Madrid, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Xeral de Vigo
🇪🇸Santiago de Compostela, A Coruña, Spain
Hospital de Elche
🇪🇸Elche, Alicante, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, Baleares, Spain
H. U. Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
H. de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital General de Castellón
🇪🇸Castelló De La Plana, Castelló, Spain
Hospital U. Marqués de Valdecilla
🇪🇸Santander, Cantabria, 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
Hospital de Mataró
🇪🇸Barcelona, Spain
Hospital U. San Cecilio
🇪🇸Granada, Spain
Hospital Virgen de las Nieves
🇪🇸Granada, Spain
Hospital U. Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Reina Sofía de Murcia
🇪🇸Murcia, Spain
Hospital U. Dr. Peset
🇪🇸Valencia, Spain
Hospital Sant Pau i Santa Tecla
🇪🇸Tarragona, Spain
Hospital Gral. U. de Valencia
🇪🇸Valencia, Spain
Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
Hospital La Fe
🇪🇸Valencia, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain