Towards HIV Functional Cure (ULTRASTOP)

This study has been completed.
Fondation Bettencourt-Schueller
Information provided by (Responsible Party):
Objectif Recherche Vaccins SIDA Identifier:
First received: May 31, 2013
Last updated: September 28, 2015
Last verified: September 2015

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:

  1. Is it possible to discontinue the treatment in chronically-infected patients with a "normal" immune system and with an undetectable HIV-DNA reservoir?
  2. 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: 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

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 ] [ 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)

Secondary Outcome Measures:
  • 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 ]

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.


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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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Please refer to this study by its identifier: NCT01876862

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
Study Director: François LECARDONNEL, MSc Objectif Recherche Vaccins SIDA
Principal Investigator: Christine KATLAMA, MD Hospital Pitié-Salpêtrière
  More Information

No publications provided

Responsible Party: Objectif Recherche Vaccins SIDA Identifier: NCT01876862     History of Changes
Other Study ID Numbers: ORVACS 012
Study First Received: May 31, 2013
Last Updated: September 28, 2015
Health Authority: France: National Agency for Drugs Safety (ANSM)

Keywords provided by Objectif Recherche Vaccins SIDA:
chronic infection
remission processed this record on October 07, 2015