Chronic HIV-1 InfectionULTRASTOPNCT01876862
Towards HIV Functional Cure
A study testing Antiretroviral treatment interruption in people with Chronic HIV-1 Infection, run by Objectif Recherche Vaccins SIDA at 2 sites in France.
Trial summary
During the ERAMUNE-01 and -02 studies, the HIV-DNA quantification in the PBMCs (Peripheral Blood Mononuclear Cells) showed showed that some patients had a very low or undetectable reservoir. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic HIV-1 Infection
- What is being tested?
- Antiretroviral treatment interruption
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesFrance
- Study dates
- Sep 2013to Jul 2015
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected patient
- CD4 count > 500 cells/mm3
- CD4/CD8 ratio > 0.9
- CD4 nadir > 300 cells/mm3
- HIV-1-RNA plasma viral load < 50 copies/mL under antiretroviral treatment for at least 2 years
- HIV-1-RNA plasma viral load < 20 copies/mL at baseline
Show all 10Show fewer
- HIV-DNA reservoir < 100 copies/million PBMCs
- Signed fully informed consent form
- Ability to attend the complete schedule of assessments and patient visits
- Patient eligible for national social insurance
Who cannot join
- Medical history of AIDS-staging event
- Antiretroviral treatment initiated during primo-infection in absence of anti-HIV antibodies (negative ELISA and Western Blot tests)
- Change in the antiretroviral treatment combination within the 3 months prior inclusion
- HIV-2 co-infection
- History of thrombocytopenia (< 100 000 cells/mm3)
- Acute neurologic event during primo-infection
Show all 19Show fewer
- Chronic and active hepatitis B as defined as positive HBs antigen or positive isolated anti-HBc antibodies
- Chronic and active hepatitis C as defined as positive anti-HCV antibodies and positive HCV-RNA PCR
- History of cancer within the 5 years prior inclusion except basocellular cutaneous cancers
- Comorbidity associated to lifespan < 12 months according investigator's opinion
- History of auto-immune disease (lupus erythematous, Hashimoto's thyroiditis, ...)
- Hemoglobin < 7 g/dL, Creatinine clearance < 60 mL/min using the MDRD formula
- Patients refusal to use a condom for any sexual relationship during the course of the study
- Refusal from women of childbearing potential to use at least one additional barrier method other than condoms
- Ongoing pregnancy as documented by a positive blood test performed at screening or later
- Lactating woman
- Psychologic unstability or patient state-of-mind incompatible with the participation in the study as evaluated by psychologist at screening
- Drug or alcohol addiction or abuse
- Concomitant participation to another trial involving any investigational treatment or device
Trial locations and contacts
2 sites in 1 country.
France2 sites
University Hospital of Bicêtre
Le Kremlin-Bicêtre, 94275
Hospital Pitié-Salpêtrière
Paris, 75013
About this study
Official title: A Pilot Study Evaluating the Maintenance of Viral Suppression After 24 Weeks of Therapeutic Interruption in Chronically HIV-1 Infected Patients With a Low Circulating HIV-DNA Reservoir
During the ERAMUNE-01 and -02 studies, the HIV-DNA quantification in the PBMCs (Peripheral Blood Mononuclear Cells) showed showed that some patients had a very low or undetectable reservoir.
Recent studies showed that a low reservoir is associated to a spontaneous virologic control in three specific categories of patients:
Read more
- "Elite Controllers": these rare patients are able to spontaneously maintain an HIV-RNA viral load below 50 copies/mL and elevated CD4 counts without any treatment. These patients belong to the B27/B57 haplotypes associated to a reduced risk of HIV contamination but these haplotypes are very rare in the global population (0,3 %)
- "Visconti" patients: early-treated patients, during the primo-infection stage. After 3 to 5 years of treatment, these patients are able to maintain an undetectable HIV-RNA viral load.
- "Salto" patients: these patients are treated a bit later compared to the Visconti cohort, when their CD4 count was above 350 cells/mm3 and their HIV-RNA viral load below 50 000 copies/mL. The follow-up of these patients showed the same capacity of control of the HIV infection for at least 2 years following treatment interruption.
Taking into account these 3 categories of patients which common characteristics is a low reservoir, our objective is to answer the 2 following questions:
- Is it possible to discontinue the treatment in chronically-infected patients with a "normal" immune system and with an undetectable HIV-DNA reservoir?
- Is a low viral reservoir predictive of a treatment-free remission of the HIV infection in chronically-infected patients?
The main objective of the proof-of-concept ERAMUNE-03 trial is to evaluate the proportion of patients in success (i.e. able to maintain a virologic and an immunologic control of the infection) after treatment discontinuation, failure is defined as:
- An HIV-RNA viral load > 400 copies/mL on 2 consecutive tests starting from Week 4
- Or CD4 count < 400 cells/mm3 on 2 consecutive measures starting from Week 4
- Or the onset of an AIDS-related event
- Conditions
- Chronic HIV-1 Infection
- Being tested
- Antiretroviral treatment interruption
- Keywords
- HIV-1, chronic infection, cure, remission
- Medical subject headings
- Persistent Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antiretroviral treatment interruptionOther
pilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption.
| Study group | Role | What they receive |
|---|---|---|
| STOP ART | Experimental | Antiretroviral treatment interruption in 3 successive groups of 5 patients.
"Zero-risk" strategy If after 8 weeks of treatment interruption, at least 1 patient from group 1 does not present any of the failure criteria, patients from group 2 will be included and their treatment interrupted. If after 8 weeks of treatment interruption, at least 2 patients from groups 1 and 2 do not present any failure criteria, patients from group 3 will be included and their treatment interrupted. Receives: Other: Antiretroviral treatment interruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients in success
Success is defined as the maintenance of the controlled viral infection after 24 weeks of therapeutic interruption. Failure is defined as:
- An HIV-1-RNA plasma viral load > 400 copies/mL starting from Week 4 as confirmed by two consecutive measures within 2 to 4 weeks
- Or a CD4 count < 400 cells/mm3 starting from Week 4 as confirmed by two consecutive measure within 2 to 4 weeks
- Or the onset of an AIDS-grading clinical event (grade B or C in the CDC classification, version 1993)
Measured: Week 24
Secondary outcomes (9)
Changes from baseline in CD4 and CD8 lymphocytes counts
Measured: Up to Week 48
Changes from baseline in immune activation and inflammation markers
Measured: Up to Week 48
Changes from baseline in anti-HIV specific T cells response
Measured: Up to Week 48
Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets
CD4 subpopulations will be live-sorted and purified. In each subset defined by surface markers, HIV-1 DNA will be quantified and transcriptional potential of HIV will be evaluated.
Measured: Up to Week 48
Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL)
Measured: Up to Week 48
Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs
Measured: Up to Week 48
Changes from baseline in the proportion of defective HIV-1 DNA
Evaluation of the stop codons in the HIV-1 DNA sequence
Measured: Up to Week 48
Changes from baseline in the plasma concentrations of antiretroviral molecules
Measured: Up to Week 48
Changes from baseline in the patient quality of life and in the disease-related symptoms
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 posted13 Jun 2013 (estimated)
- Study startSep 2013
- Primary completionDec 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic 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
- Interventional
- Phase
- Phase N/A
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Objectif Recherche Vaccins SIDA
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation Bettencourt-Schueller
- Responsible party
- Sponsor
- Investigators
- François LECARDONNEL, MSc, Study director, Objectif Recherche Vaccins SIDAChristine KATLAMA, MD, Principal investigator, Hospital Pitié-Salpêtrière
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01876862
- Sponsor's protocol ID
- ORVACS 012
- Acronym
- ULTRASTOP
- Status last verified
- Sep 2015
- First submitted
- 31 May 2013
- Last updated
- 29 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Evaluating the Maintenance of Viral Suppression After 24 Weeks of Therapeutic Interruption in Chronically HIV-1 Infected Patients With a Low Circulating HIV-DNA Reservoir
- ClinicalTrials.gov ID
- NCT01876862
- Acronym / sponsor ID
- ULTRASTOP / ORVACS 012
- Conditions
- Chronic HIV-1 Infection
- Keywords
- HIV-1, chronic infection, cure, remission
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Objectif Recherche Vaccins SIDAUniversity, hospital or other
- Collaborators
- Fondation Bettencourt-Schueller
- Study start
- Sep 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 13 Jun 2013 (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.
During the ERAMUNE-01 and -02 studies, the HIV-DNA quantification in the PBMCs (Peripheral Blood Mononuclear Cells) showed showed that some patients had a very low or undetectable reservoir.
Recent studies showed that a low reservoir is associated to a spontaneous virologic control in three specific categories of patients:
- "Elite Controllers": these rare patients are able to spontaneously maintain an HIV-RNA viral load below 50 copies/mL and elevated CD4 counts without any treatment. These patients belong to the B27/B57 haplotypes associated to a reduced risk of HIV contamination but these haplotypes are very rare in the global population (0,3 %)
- "Visconti" patients: early-treated patients, during the primo-infection stage. After 3 to 5 years of treatment, these patients are able to maintain an undetectable HIV-RNA viral load.
- "Salto" patients: these patients are treated a bit later compared to the Visconti cohort, when their CD4 count was above 350 cells/mm3 and their HIV-RNA viral load below 50 000 copies/mL. The follow-up of these patients showed the same capacity of control of the HIV infection for at least 2 years following treatment interruption.
Taking into account these 3 categories of patients which common characteristics is a low reservoir, our objective is to answer the 2 following questions:
- Is it possible to discontinue the treatment in chronically-infected patients with a "normal" immune system and with an undetectable HIV-DNA reservoir?
- Is a low viral reservoir predictive of a treatment-free remission of the HIV infection in chronically-infected patients?
The main objective of the proof-of-concept ERAMUNE-03 trial is to evaluate the proportion of patients in success (i.e. able to maintain a virologic and an immunologic control of the infection) after treatment discontinuation, failure is defined as:
- An HIV-RNA viral load > 400 copies/mL on 2 consecutive tests starting from Week 4
- Or CD4 count < 400 cells/mm3 on 2 consecutive measures starting from Week 4
- Or the onset of an AIDS-related event
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| STOP ART | Experimental | Other: Antiretroviral treatment interruptionAntiretroviral treatment interruption in 3 successive groups of 5 patients. "Zero-risk" strategy If after 8 weeks of treatment interruption, at least 1 patient from group 1 does not present any of the failure criteria, patients from group 2 will be included and their treatment interrupted. If after 8 weeks of treatment interruption, at least 2 patients from groups 1 and 2 do not present any failure criteria, patients from group 3 will be included and their treatment interrupted. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- HIV-1 infected patient
- CD4 count > 500 cells/mm3
- CD4/CD8 ratio > 0.9
- CD4 nadir > 300 cells/mm3
- HIV-1-RNA plasma viral load < 50 copies/mL under antiretroviral treatment for at least 2 years
Key exclusion criteria (19 listed)
- Medical history of AIDS-staging event
- Antiretroviral treatment initiated during primo-infection in absence of anti-HIV antibodies (negative ELISA and Western Blot tests)
- Change in the antiretroviral treatment combination within the 3 months prior inclusion
- HIV-2 co-infection
- History of thrombocytopenia (< 100 000 cells/mm3)
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 |
|---|---|---|
| Antiretroviral treatment interruptionpilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption. | Other | STOP ART |
Primary outcome
Proportion of patients in success
Time frame: Week 24
Success is defined as the maintenance of the controlled viral infection after 24 weeks of therapeutic interruption. Failure is defined as: * An HIV-1-RNA plasma viral load > 400 copies/mL starting from Week 4 as confirmed by two consecutive measures within 2 to 4 weeks * Or a CD4 count < 400 cells/mm3 starting from Week 4 as confirmed by two consecutive measure within 2 to 4 weeks * Or the onset of an AIDS-grading clinical event (grade B or C in the CDC classification, version 1993)
9 secondary outcomes
Changes from baseline in CD4 and CD8 lymphocytes counts
Time frame: Up to Week 48
Changes from baseline in immune activation and inflammation markers
Time frame: Up to Week 48
Changes from baseline in anti-HIV specific T cells response
Time frame: Up to Week 48
Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets
Time frame: Up to Week 48
Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL)
Time frame: Up to Week 48
Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs
Time frame: Up to Week 48
Changes from baseline in the proportion of defective HIV-1 DNA
Time frame: Up to Week 48
Changes from baseline in the plasma concentrations of antiretroviral molecules
Time frame: Up to Week 48
Changes from baseline in the patient quality of life and in the disease-related symptoms
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 29 Sep 2015.
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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.
François LECARDONNEL, MSc study director
Objectif Recherche Vaccins SIDA
Christine KATLAMA, MD principal investigator
Hospital Pitié-Salpêtrière
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Antiretroviral treatment interruption in people with Chronic HIV-1 Infection, run by Objectif Recherche Vaccins SIDA at 2 sites 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 10 inclusion and 19 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 29 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Proportion of patients in success (time frame: Week 24). 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 29 Sep 2015.