Skip to main content
OpenTrials
Completed

NCT Number: NCT01876862

Towards HIV Functional Cure

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

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Chronic HIV-1 Infection Disease Attributes Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Persistent Infection

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital of Bicêtre, Le Kremlin-Bicêtre, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Antiretroviral treatment interruption

Other

pilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption.

Primary outcomes

  1. 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 outcomes

  1. Changes from baseline in CD4 and CD8 lymphocytes counts

    Time frame: Up to Week 48

  2. Changes from baseline in immune activation and inflammation markers

    Time frame: Up to Week 48

  3. Changes from baseline in anti-HIV specific T cells response

    Time frame: Up to Week 48

  4. 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.

  5. Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL)

    Time frame: Up to Week 48

  6. Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs

    Time frame: Up to Week 48

  7. 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

  8. Changes from baseline in the plasma concentrations of antiretroviral molecules

    Time frame: Up to Week 48

  9. Changes from baseline in the patient quality of life and in the disease-related symptoms

    Time frame: Up to Week 48

Sponsors and collaborators

Lead sponsor

Objectif Recherche Vaccins SIDA

Other

Collaborators

  • Fondation Bettencourt-Schueller

Registry information

Official study 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

Acronym: ULTRASTOP

Important dates

Study start
2013
Primary completion
2014
Study completion
2015
First posted
Jun 13, 2013
Registry last updated
Sep 29, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.