Chronic HIV-1 Infection
Conditions
Keywords
HIV-1, chronic infection, cure, remission
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
Interventions
pilot study in chronically HIV-infected patients with an ultralow HIV reservoir undergoing treatment-interruption.
Sponsors
Fondation Bettencourt-Schueller
Objectif Recherche Vaccins SIDA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients in success | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL) | Up to Week 48 | — |
| Changes from baseline in CD4 and CD8 lymphocytes counts | Up to Week 48 | — |
| Changes from baseline in the proportion of defective HIV-1 DNA | Up to Week 48 | Evaluation of the stop codons in the HIV-1 DNA sequence |
| Changes from baseline in the plasma concentrations of antiretroviral molecules | Up to Week 48 | — |
| Changes from baseline in the patient quality of life and in the disease-related symptoms | Up to Week 48 | — |
| Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs | Up to Week 48 | — |
Countries
France
Outcome results
None listed