Towards HIV Functional Cure (ULTRASTOP)
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:||Endpoint Classification: Safety/Efficacy Study
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|
- Proportion of patients in success [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
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)
- Changes from baseline in CD4 and CD8 lymphocytes counts [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
- Changes from baseline in immune activation and inflammation markers [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
- Changes from baseline in anti-HIV specific T cells response [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
- Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
- Changes from baseline in the proportion of defective HIV-1 DNA [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Changes from baseline in the patient quality of life and in the disease-related symptoms [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
No Intervention: 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|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01876862
|Contact: François LECARDONNEL, MScemail@example.com|
|University Hospital of Bicêtre||Not yet recruiting|
|Le Kremlin Bicêtre, France, 94275|
|Contact: Olivier LAMBOTTE, MD +33145212783 firstname.lastname@example.org|
|Contact: Katia BOURDIC +33145216316 email@example.com|
|Principal Investigator: Olivier LAMBOTTE, MD|
|Hospital Pitié-Salpêtrière||Not yet recruiting|
|Paris, France, 75013|
|Contact: Christine KATLAMA, MD +33142160130 firstname.lastname@example.org|
|Contact: Ruxandra CALIN, MD +33142160129 email@example.com|
|Principal Investigator: Christine KATLAMA, MD|
|Sub-Investigator: Roland TUBIANA, MD|
|Sub-Investigator: Marc-Antoine VALANTIN, MD|
|Sub-Investigator: Nadine KTORZA, MD|
|Sub-Investigator: Luminita SCHNEIDER, MD|
|Study Director:||François LECARDONNEL, MSc||Objectif Recherche Vaccins SIDA|
|Principal Investigator:||Christine KATLAMA, MD||Hospital Pitié-Salpêtrière|