HIVPhase 4NCT01378910
Genotypic Tropism Testing In Proviral Dna To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
A Phase 4 study testing Unique in people with HIV, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 24 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HIV
- What is being tested?
- Unique
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 24 sitesSpain
- Study dates
- Jun 2011to May 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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).
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Spain24 sites
Hospital Gral. U. de Alicante
Alicante, 03010
H. U. Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Vall d'Hebron
Barcelona, 08035
Hospital de Mataró
Barcelona, 08304
Hospital de Cruces
Bilbao, Vizcaya, 48903
Hospital Sta. Lucía/ H. Sta. Mª del Rosell
Cartagena, Murcia, 30203
Hospital General de Castellón
Castellon, Castelló, 12004
Hospital de Elche
Elche, Alicante, 03203
Hospital Virgen de las Nieves
Granada, 18014
Hospital U. San Cecilio
Granada, 28012
H. de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital U. Gregorio Marañón
Madrid, 28007
Hospital Carlos III
Madrid, 28029
Hospital Ramón y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
Hospital Reina Sofía de Murcia
Murcia, 30003
Hospital Son Espases
Palma de Mallorca, Balearic Islands, 07011
Hospital U. Marqués de Valdecilla
Santander, Cantabria, 39011
Hospital Xeral de Vigo
Santiago de Compostela, A Coruña, 15781
Hospital Sant Pau i Santa Tecla
Tarragona, 43007
Hospital La Fe
Valencia, 46009
Hospital Gral. U. de Valencia
Valencia, 46014
Hospital Arnau de Vilanova
Valencia, 46015
Hospital U. Dr. Peset
Valencia, 46017
About this study
Official title: Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
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.
Read the 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.
- Conditions
- HIV
- Being tested
- Unique
- Keywords
- HIV, TROPISM, PBMC, GENOTYPE, 454 SEQUENCING
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UniqueDrug
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
| Study group | Role | What they receive |
|---|---|---|
| Change of 3rd drug to maraviroc | Experimental | Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc) Receives: Drug: Unique |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with viral load under 50 copies/mL
Measured: Week 48
Secondary outcomes (36)
Percentage of patients without confirmed virological failure.
To evaluate other aspects related to maintanence of virological response.
Measured: Up to week 48
Time to loss of virological response (TLOVR) < 200 copies/mL
To evaluate other aspects related to maintanence of virological response.
Measured: Up to week 48
Time to loss of virological response (TLOVR) < 50 copies/mL
To evaluate other aspects related to maintanence of virological response.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: From baseline to week 48.
Median change of HDL cholesterol.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of LDL cholesterol.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of triglycerides
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of AST serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of ALT serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of alkaline phosphatase serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Median change of total bilirubin serum levels.
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: From Baseline to week 48.
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 4
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 12
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 24
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 36
Cumulative number of adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 48
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 4
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 12
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 24
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: Week 36
Cumulative number of grade 3-4 adverse events
To evaluate the tolerability and safety with CCR5 antagonist containing regimen
Measured: 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
Measured: Up to week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionApr 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378910
- Sponsor's protocol ID
- PROTEST
- Status last verified
- Jul 2014
- First submitted
- 17 Jun 2011
- Last updated
- 14 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
- ClinicalTrials.gov ID
- NCT01378910
- Acronym / sponsor ID
- PROTEST
- Conditions
- HIV
- Keywords
- HIV, TROPISM, PBMC, GENOTYPE, 454 SEQUENCING
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 23 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Change of 3rd drug to maraviroc | Experimental | Drug: UniqueChange of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UniqueChange of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc) | Drug | Change of 3rd drug to maraviroc |
Primary outcome
Percentage of patients with viral load under 50 copies/mL
Time frame: Week 48
36 secondary outcomes
Percentage of patients without confirmed virological failure.
Time frame: Up to week 48
Time to loss of virological response (TLOVR) < 200 copies/mL
Time frame: Up to week 48
Time to loss of virological response (TLOVR) < 50 copies/mL
Time frame: Up to week 48
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Time frame: Week 12
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Time frame: Week 24
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Time frame: Week 36
Proportion of patients treated with maraviroc with viral load under 50 copies/mL
Time frame: Week 48
Time to treatment discontinuation, overall, and due to factors other than loss 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.
Time frame: Week 48
Level of X4 viruses by detected by population sequencing.
Time frame: Screening (up to 48 weeks)
Level of X4 viruses by detected by population sequencing.
Time frame: Week 12
Level of X4 viruses by detected by population sequencing.
Time frame: Week 48
Level of X4 viruses by detected by deep sequencing.
Time frame: Screening (up to 48 weeks)
Level of X4 viruses by detected by deep sequencing.
Time frame: Week 12
Level of X4 viruses by detected by deep sequencing.
Time frame: Week 48
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
Time frame: In case of virological failure (week 12 up to virological failure)
Median change of total cholesterol.
Time frame: From baseline to week 48.
Median change of HDL cholesterol.
Time frame: From Baseline to week 48.
Median change of LDL cholesterol.
Time frame: From Baseline to week 48.
Median change of triglycerides
Time frame: From Baseline to week 48.
Median change of AST serum levels.
Time frame: From Baseline to week 48.
Median change of ALT serum levels.
Time frame: From Baseline to week 48.
Median change of alkaline phosphatase serum levels.
Time frame: From Baseline to week 48.
Median change of total bilirubin serum levels.
Time frame: From Baseline to week 48.
Cumulative number of adverse events
Time frame: Week 4
Cumulative number of adverse events
Time frame: Week 12
Cumulative number of adverse events
Time frame: Week 24
Cumulative number of adverse events
Time frame: Week 36
Cumulative number of adverse events
Time frame: Week 48
Cumulative number of grade 3-4 adverse events
Time frame: Week 4
Cumulative number of grade 3-4 adverse events
Time frame: Week 12
Cumulative number of grade 3-4 adverse events
Time frame: Week 24
Cumulative number of grade 3-4 adverse events
Time frame: Week 36
Cumulative number of grade 3-4 adverse events
Time frame: Week 48
Proportion of patients withdrawn from the study and reason for study withdrawal
Time frame: Up to week 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Unique in people with HIV, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 24 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with viral load under 50 copies/mL (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.