Towards HIV Functional Cure (ULTRASTOP)

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Condition or disease	Intervention/treatment	Phase
Chronic HIV-1 Infection	Other: Antiretroviral treatment interruption	Not Applicable

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	September 2013
Actual Primary Completion Date :	December 2014
Actual Study Completion Date :	July 2015

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm

Intervention/treatment

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.

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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 Outcome Measures :

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 ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

France
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

Investigators

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

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Objectif Recherche Vaccins SIDA
ClinicalTrials.gov Identifier:	NCT01876862 History of Changes
Other Study ID Numbers:	ORVACS 012
First Posted:	June 13, 2013
Last Update Posted:	September 29, 2015
Last Verified:	September 2015

Keywords provided by Objectif Recherche Vaccins SIDA:

HIV-1; chronic infection; cure; remission