Clinical trial NCT01876862: Towards HIV Functional Cure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic HIV-1 Infection
Keywords: HIV-1
chronic infection
cure
remission
Lead sponsor: Objectif Recherche Vaccins SIDA
Sponsor class: OTHER
Collaborators: name: Fondation Bettencourt-Schueller
First posted: 2013-06-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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


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

Primary outcomes:
measure: Proportion of patients in success
timeFrame: Week 24
Secondary outcomes:
measure: Changes from baseline in CD4 and CD8 lymphocytes counts
timeFrame: Up to Week 48
measure: Changes from baseline in immune activation and inflammation markers
timeFrame: Up to Week 48
measure: Changes from baseline in anti-HIV specific T cells response
timeFrame: Up to Week 48
measure: Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets
timeFrame: Up to Week 48
measure: Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL)
timeFrame: Up to Week 48
measure: Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs
timeFrame: Up to Week 48
measure: Changes from baseline in the proportion of defective HIV-1 DNA
timeFrame: Up to Week 48
measure: Changes from baseline in the plasma concentrations of antiretroviral molecules
timeFrame: Up to Week 48
measure: Changes from baseline in the patient quality of life and in the disease-related symptoms
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: University Hospital of Bicêtre
city: Paris
country: France
facility: Hospital Pitié-Salpêtrière
Study officials:
affiliation: Objectif Recherche Vaccins SIDA
name: François LECARDONNEL, MSc
role: STUDY_DIRECTOR
affiliation: Hospital Pitié-Salpêtrière
name: Christine KATLAMA, MD
role: PRINCIPAL_INVESTIGATOR
References: