Towards HIV Functional Cure (ULTRASTOP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01876862
Recruitment Status : Completed
First Posted : June 13, 2013
Last Update Posted : September 29, 2015
Fondation Bettencourt-Schueller
Information provided by (Responsible Party):
Objectif Recherche Vaccins SIDA

May 31, 2013
June 13, 2013
September 29, 2015
September 2013
December 2014   (Final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01876862 on Archive Site
  • 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 ]
Same as current
Not Provided
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Towards HIV Functional Cure
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:

  • "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
Not Provided
Not Applicable
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Chronic HIV-1 Infection
Other: Antiretroviral treatment interruption
pilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption.
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.

Intervention: Other: Antiretroviral treatment interruption
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
July 2015
December 2014   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Not Provided
Not Provided
Objectif Recherche Vaccins SIDA
Objectif Recherche Vaccins SIDA
Fondation Bettencourt-Schueller
Study Director: François LECARDONNEL, MSc Objectif Recherche Vaccins SIDA
Principal Investigator: Christine KATLAMA, MD Hospital Pitié-Salpêtrière
Objectif Recherche Vaccins SIDA
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP