towards hiv functional cure

Conditions: Chronic HIV-1 Infection

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

Keywords: hiv-1 chronic infection cure remission