Towards HIV Functional Cure

NCT01876862 | Completed DMC

• 1 other identifier: ORVACS 012
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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:
• 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?
• 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

Keywords

HIV-1; chronic infection; cure; remission

Outcome Measures

Primary Outcomes (1)

• Proportion of patients in success

  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)

  Week 24

Secondary Outcomes (9)

• Changes from baseline in CD4 and CD8 lymphocytes counts

  Up to Week 48

• Changes from baseline in immune activation and inflammation markers

  Up to Week 48

• Changes from baseline in anti-HIV specific T cells response

  Up to Week 48

• Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets

  Up to Week 48

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

  Up to Week 48

Study Arms (1)

STOP ART

EXPERIMENTAL

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

Interventions

Antiretroviral treatment interruption OTHER

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

STOP ART

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Medical history of AIDS-staging event
• Antiretroviral treatment initiated during primo-infection in absence of anti-HIV antibodies (negative ELISA and Western Blot tests)
• 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
• 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

Sponsors & Collaborators

• Objectif Recherche Vaccins SIDA: lead
• Fondation Bettencourt-Schueller: collaborator

Study Sites (2)

University Hospital of Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Hospital Pitié-Salpêtrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Persistent Infection

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• François LECARDONNEL, MSc

  Objectif Recherche Vaccins SIDA

  STUDY DIRECTOR

• Christine KATLAMA, MD

  Hospital Pitié-Salpêtrière

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2013
• First Posted: June 13, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: September 29, 2015

Record last verified: 2015-09

Locations

FR (2)