Towards HIV Functional Cure

NCT ID: NCT01876862

Last Updated: 2015-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2015-07-31

Brief Summary

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

Conditions

Chronic HIV-1 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Antiretroviral treatment interruption

Intervention Type: OTHER

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

Interventions

Antiretroviral treatment interruption

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

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation Bettencourt-Schueller

UNKNOWN

Sponsor Role: collaborator

Objectif Recherche Vaccins SIDA

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François LECARDONNEL, MSc

Role: STUDY_DIRECTOR

Objectif Recherche Vaccins SIDA

Christine KATLAMA, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Pitié-Salpêtrière

Locations

University Hospital of Bicêtre

Le Kremlin-Bicêtre, , France

Hospital Pitié-Salpêtrière

Paris, , France

Countries

France

Other Identifiers

ORVACS 012

Identifier Type: -

Identifier Source: org_study_id