HIV-1-infectionMUTARESERVOIRNCT04448158
Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy
An observational study of HIV-1-infection, run by Association de Recherche en Virologie et Dermatologie at 1 site in France.
Trial summary
In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Genotypic Resistance Test
- How many people
- 79 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jul 2020to 1 Jul 2021
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The studied population will be composed of followed HIV infected patients of the center, of whom approximately 90% are under treatment and virologically suppressed, consecutively selected (in an anti-chronological order on the sample failure date) until gathering the requested number of patients meeting the eligibility criteria.
Who may be able to join
- HIV-1 infected
- Age ≥ 18 years
- Genotypic resistance test performed at time of failure and harboring at least M184V
- Fully suppressed HIV viral load for at least 5 or 10 years.
- Triple therapy or 2 drug regimen during the entire follow-up
- Availability of at least 1 stored whole blood sample /year
Who cannot join
- No genotypic resistance test available at time of failure.
Trial locations and contacts
1 site in 1 country.
About this study
In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization.
Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for an unknown duration and reemerge in case of therapeutic selective pressure.
Read more
There is a need to assess the dynamic of archived Drug resistance associated mutations (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in the perspective of ARVs recycling.
The investigators postulate that it could be interesting in the future to recycle ARV drugs (that where classified as "resistant" in the past) in subsequent regimen. The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V).
Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART.
- Conditions
- HIV-1-infection
- Being tested
- Genotypic Resistance Test
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genotypic Resistance TestDiagnostic test
A Genotypic Resistance Test by Sanger sequencing will be done after the period of virological suppression.
- If M184V is still present no additional test will be performed.
- If M184V is absent, we will go back in the previous samples (one per year) to determine the time point where the mutation has been cleared by sanger and UDS sequencing.
| Study group | Role | What they receive |
|---|---|---|
| 5 years of virological suppression | - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years Receives: Diagnostic Test: Genotypic Resistance Test | |
| 10 years of virological suppression | - Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years Receives: Diagnostic Test: Genotypic Resistance Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of M184V mutation
The persistence of M184V resistance mutation is defined by the detection of this mutation in 2 consecutive samples by Sanger and by a percentage of this mutation > 1% in 2 consecutive samples by UltraDeep Sequencing. The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation > 1% in a sample and a percentage < 1% in the subsequent sample.
Measured: One measure per year
Percentage of M184V mutation
Percentage detected by UltraDeep Sequencing
Measured: One measure per year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start1 Jul 2020
- Primary completion1 May 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Association de Recherche en Virologie et Dermatologie
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare
- Responsible party
- Sponsor
- Investigators
- Anne-Geneviève MARCELIN, Principal investigator, Sorbonne University; APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04448158
- Sponsor's protocol ID
- ARVD-MUTARESERVOIR
- Acronym
- MUTARESERVOIR
- Status last verified
- Feb 2023
- First submitted
- 23 Jun 2020
- Last updated
- 10 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT04448158
- Acronym / sponsor ID
- MUTARESERVOIR / ARVD-MUTARESERVOIR
- Conditions
- HIV-1-infection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Association de Recherche en Virologie et DermatologieUniversity, hospital or other
- Collaborators
- ViiV Healthcare
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 May 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 25 Jun 2020 (actual)
- 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.
In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization.
Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for an unknown duration and reemerge in case of therapeutic selective pressure.
There is a need to assess the dynamic of archived Drug resistance associated mutations (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in the perspective of ARVs recycling.
The investigators postulate that it could be interesting in the future to recycle ARV drugs (that where classified as "resistant" in the past) in subsequent regimen. The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V).
Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5 years of virological suppression | – | Diagnostic Test: Genotypic Resistance Test- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 5 years |
| 10 years of virological suppression | – | Diagnostic Test: Genotypic Resistance Test- Patients harboring a fully suppressed HIV-1 plasma viral load for at least 10 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The studied population will be composed of followed HIV infected patients of the center, of whom approximately 90% are under treatment and virologically suppressed, consecutively selected (in an anti-chronological order on the sample failure date) until gathering the requested number of patients meeting the eligibility criteria.
Key inclusion criteria (6 listed)
- HIV-1 infected
- Age ≥ 18 years
- Genotypic resistance test performed at time of failure and harboring at least M184V
- Fully suppressed HIV viral load for at least 5 or 10 years.
- Triple therapy or 2 drug regimen during the entire follow-up
Key exclusion criteria (1 listed)
- No genotypic resistance test available at time of failure.
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 |
|---|---|---|
| Genotypic Resistance TestA Genotypic Resistance Test by Sanger sequencing will be done after the period of virological suppression. * If M184V is still present no additional test will be performed. * If M184V is absent, we will go back in the previous samples (one per year) to determine the time point where the mutation has been cleared by sanger and UDS sequencing. | Diagnostic test | 10 years of virological suppression, 5 years of virological suppression |
Primary outcome
Detection of M184V mutation
Time frame: One measure per year
The persistence of M184V resistance mutation is defined by the detection of this mutation in 2 consecutive samples by Sanger and by a percentage of this mutation > 1% in 2 consecutive samples by UltraDeep Sequencing. The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation > 1% in a sample and a percentage < 1% in the subsequent sample.
Percentage of M184V mutation
Time frame: One measure per year
Percentage detected by UltraDeep Sequencing
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 10 Feb 2023.
- Individual participant dataSharing planned: No
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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.
Anne-Geneviève MARCELIN principal investigator
Sorbonne University; APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by Association de Recherche en Virologie et Dermatologie at 1 site in France.
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 6 inclusion and 1 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 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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.
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?
Detection of M184V mutation (time frame: One measure per year). The study lists 2 primary outcomes in all. 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 10 Feb 2023.