Co-adaptation Between Human Immunodeficiency Virus (HIV) and Cluster of Differentiation 8 (CD8) Cellular Immunity
Condition: HIV Infection
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Observational

Summary: 
      The objective is to characterize the viral evolution and viral factors determining HIV
      virulence, the evolution of the HIV reservoir in PBMC and the co-evolution of anti-HIV CD8 T
      cell repertoires. The coordinated study of virus evolution, host responses and identification
      of genetic determinants of virulence should allow to better understand mechanisms of HIV
      pathogenicity and persistence of mutations in viral reservoirs.
    

Detailed description: 
      The importance of the still unmet challenges raised by researches on the eradication of the
      HIV reservoirs and by the need for developing efficient vaccines against HIV, imposes a much
      deeper understanding the molecular mechanisms regulating the co-evolution and the
      co-adaptation between HIV and its host during the natural course of the disease an during
      treatment. The unique cell collection established 27 years ago in an ANRS cohort (ImmunoCo)
      and the new methods of ultra deep sequencing, or " next generation sequencing", allow to
      produce innovative analysis of the HIV variability and of reservoirs as well as of the
      repertoires used by CD8 T cells responses to provide new insights in the very long term
      relationships between the virus and its host. The objective is to progress at unprecedented
      levels in the understanding of these mechanisms thanks to the unique opportunity offered by
      this Immunoco cohort initially composed of 152 patients infected by HIV, most of them
      untreated when recruited from 1991 to 97 at Pitié-Salpêtrière hospital, with 28 subjects
      still followed in this hospital and efficiently treated for the last 15 years. The ImmunoCo
      cohort had initially been set up to study the characteristics of the cytotoxic T lymphocyte
      (CTL) responses to HIV with disease progression. This exceptional and still available 1991-97
      cell collection enriched of extra samples from 1988 to nowadays, allow us to perform a
      retrospective longitudinal analysis over 27 years in the 28 patients still followed-up, with
      a new blood sampling in 2016. The project involves 5 highly experienced teams and aims at
      characterizing in parallel: 1) the viral evolution and viral factors determining virulence,
      as markers predicting progression of infection, by performing an ultra deep sequencing of the
      whole HIV genome and of viral variants archived in blood mononuclear cells (PBMC), and 2) the
      evolution of the reservoir in PBMC and of the distribution of variants archived in those
      reservoirs over time, in relationship with exposure to the various selective pressures due to
      CTL or antiretroviral therapy (ART), 3) the co-evolution of anti-HIV CD8 T cell repertoires:
      the hypothesis is that the emergence of new CD8 T clonotypes displaying a great sensibility
      for variant antigens, or a cross-reactivity able to recognize similarly wild-type and mutant
      epitopes allow an efficient long term control of viral replication, and that cell loss by
      clonal exhaustion is associated to disease progression. The coordinated study of virus
      evolution, host responses and identification of genetic determinants of virulence should
      allow to better understand mechanisms of HIV pathogenicity and persistence of mutations in
      viral reservoirs, especially of defective mutants or resistant mutants to ART, as well as the
      co-adaptation of CD8 T cell repertoires and of viral variability determining the capacities
      of viral control by anti-HIV CD8 T cells. Altogether these results should open new strategies
      for inhibiting viral replication and for controlling viral reservoirs for therapeutic and
      vaccinal perspectives.
    

Intervention name(s): Non interventional study
Intervention type(s): Other
Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Patients infected with HIV included in the ANRS Immunoco cohort.
      
Biospecimen description: 
      frozen PBMC
    
Keywords: HIV infection