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Towards HIV Functional Cure (ULTRASTOP)
This study has been completed.
Sponsor:
Objectif Recherche Vaccins SIDA
Collaborator:
Fondation Bettencourt-Schueller
Information provided by (Responsible Party):
Objectif Recherche Vaccins SIDA
ClinicalTrials.gov Identifier:
NCT01876862
First received: May 31, 2013
Last updated: September 28, 2015
Last verified: September 2015
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Purpose
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
| Condition | Intervention |
|---|---|
| Chronic HIV-1 Infection | Other: Antiretroviral treatment interruption |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label |
| 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 |
Resource links provided by NLM:
Further study details as provided by Objectif Recherche Vaccins SIDA:
Primary Outcome Measures:
- 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)
Secondary Outcome Measures:
- 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 ]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.
- 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 ]Evaluation of the stop codons in the HIV-1 DNA sequence
- 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 ]
| Enrollment: | 15 |
| Study Start Date: | September 2013 |
| Study Completion Date: | July 2015 |
| Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: STOP ART
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. |
Other: Antiretroviral treatment interruption
pilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption.
|
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01876862
Please refer to this study by its ClinicalTrials.gov identifier: NCT01876862
Locations
| France | |
| University Hospital of Bicêtre | |
| Le Kremlin Bicêtre, France, 94275 | |
| Hospital Pitié-Salpêtrière | |
| Paris, France, 75013 | |
Sponsors and Collaborators
Objectif Recherche Vaccins SIDA
Fondation Bettencourt-Schueller
Investigators
| Study Director: | François LECARDONNEL, MSc | Objectif Recherche Vaccins SIDA |
| Principal Investigator: | Christine KATLAMA, MD | Hospital Pitié-Salpêtrière |
More Information
| Responsible Party: | Objectif Recherche Vaccins SIDA |
| ClinicalTrials.gov Identifier: | NCT01876862 History of Changes |
| Other Study ID Numbers: |
ORVACS 012 |
| Study First Received: | May 31, 2013 |
| Last Updated: | September 28, 2015 |
Keywords provided by Objectif Recherche Vaccins SIDA:
|
HIV-1 chronic infection cure remission |
ClinicalTrials.gov processed this record on July 17, 2017