Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
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ClinicalTrials.gov Identifier: NCT01378910 |
Recruitment Status
:
Completed
First Posted
: June 23, 2011
Last Update Posted
: July 3, 2014
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV | Drug: Unique | Phase 4 |
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 (Clinical Trial) |
Actual Enrollment : | 74 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia |
Study Start Date : | June 2011 |
Actual Primary Completion Date : | April 2014 |
Actual Study Completion Date : | May 2014 |

Arm | Intervention/treatment |
---|---|
Experimental: Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
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Drug: Unique
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
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- Percentage of patients with viral load under 50 copies/mL [ Time Frame: Week 48 ]
- Percentage of patients without confirmed virological failure. [ Time Frame: Up to week 48 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]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 ]To evaluate changes in HIV tropism
- Level of X4 viruses by detected by population sequencing. [ Time Frame: Screening (up to 48 weeks) ]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 ]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 ]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) ]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 ]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 ]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 ]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) ]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. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Median change of HDL cholesterol. [ Time Frame: From Baseline to week 48. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Median change of LDL cholesterol. [ Time Frame: From Baseline to week 48. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Median change of triglycerides [ Time Frame: From Baseline to week 48. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Median change of AST serum levels. [ Time Frame: From Baseline to week 48. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Median change of ALT serum levels. [ Time Frame: From Baseline to week 48. ]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. ]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. ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of adverse events [ Time Frame: Week 4 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of adverse events [ Time Frame: Week 12 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of adverse events [ Time Frame: Week 24 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of adverse events [ Time Frame: Week 36 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of adverse events [ Time Frame: Week 48 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of grade 3-4 adverse events [ Time Frame: Week 4 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of grade 3-4 adverse events [ Time Frame: Week 12 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of grade 3-4 adverse events [ Time Frame: Week 24 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of grade 3-4 adverse events [ Time Frame: Week 36 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen
- Cumulative number of grade 3-4 adverse events [ Time Frame: 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 [ Time Frame: Up to week 48 ]To evaluate the tolerability and safety with CCR5 antagonist containing regimen

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01378910
Spain | |
Hospital Xeral de Vigo | |
Santiago de Compostela, A Coruña, Spain, 15781 | |
Hospital de Elche | |
Elche, Alicante, Spain, 03203 | |
Hospital Son Espases | |
Palma de Mallorca, Baleares, Spain, 07011 | |
H. U. Germans Trias i Pujol | |
Badalona, Barcelona, Spain, 08916 | |
H. de Bellvitge | |
Hospitalet de Llobregat, Barcelona, Spain, 08907 | |
Hospital U. Marqués de Valdecilla | |
Santander, Cantabria, Spain, 39011 | |
Hospital Sta. Lucía/ H. Sta. Mª del Rosell | |
Cartagena, Murcia, Spain, 30203 | |
Hospital General de Castellón | |
Castellón, Valencia, Spain, 12004 | |
Hospital de Cruces | |
Bilbao, Vizcaya, Spain, 48903 | |
Hospital Gral. U. de Alicante | |
Alicante, Spain, 03010 | |
Hospital Vall d'Hebron | |
Barcelona, Spain, 08035 | |
Hospital de Mataró | |
Barcelona, Spain, 08304 | |
Hospital Virgen de las Nieves | |
Granada, Spain, 18014 | |
Hospital U. San Cecilio | |
Granada, Spain, 28012 | |
Hospital U. Gregorio Marañón | |
Madrid, Spain, 28007 | |
Hospital Carlos III | |
Madrid, Spain, 28029 | |
Hospital Ramón y Cajal | |
Madrid, Spain, 28034 | |
Hospital Clínico San Carlos | |
Madrid, Spain, 28040 | |
Hospital Reina Sofía de Murcia | |
Murcia, Spain, 30003 | |
Hospital Sant Pau i Santa Tecla | |
Tarragona, Spain, 43007 | |
Hospital La Fe | |
Valencia, Spain, 46009 | |
Hospital Gral. U. de Valencia | |
Valencia, Spain, 46014 | |
Hospital Arnau de Vilanova | |
Valencia, Spain, 46015 | |
Hospital U. Dr. Peset | |
Valencia, Spain, 46017 |
Responsible Party: | Fundacio Lluita Contra la SIDA |
ClinicalTrials.gov Identifier: | NCT01378910 History of Changes |
Other Study ID Numbers: |
PROTEST |
First Posted: | June 23, 2011 Key Record Dates |
Last Update Posted: | July 3, 2014 |
Last Verified: | July 2014 |
Keywords provided by Fundacio Lluita Contra la SIDA:
HIV TROPISM PBMC GENOTYPE 454 SEQUENCING |
Additional relevant MeSH terms:
Viremia Virus Diseases Sepsis Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Maraviroc Integrase Inhibitors |
CCR5 Receptor Antagonists Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors |