Explore the role of NK cells in post-treatment control of HIV-1 infection: impact of genetic background and early treatment initiation

Antiretroviral therapy (ART) blocks HIV replication but cannot eliminate viral reservoirs that originate viral rebound if ART is discontinued.

However, the host laboratory originally described some individuals, post-treatment controllers (PTC), capable to durably control viremia after ART discontinuation.

More recently, the group has found that HLA B*35 alleles (usually associated with rapid progression in the absence of ART) are paradoxicaly overrepresented in PTCs and are accompanied with an MHC immunogenetic fingerprint (termed Bw4TTC2 by the lab), related to KIR-education of NK cells.

The proposed work aims to better characterize transcriptional and functional signatures of NK cells in PTC and other people with HIV (PWH), their evolution since primary infection, during ART, and after ART discontinuation, and in regard of immunogenetic factors.

These will be done in three different settings: (i) crossectional analysis in groups of people with well-characterized HIV status; (ii) longitudinal samples from the biobank of the primate-VISCONTI study (pVISCONTI); (iii) prospective study of samples from individuals on ART since primary HIV infection and carrying B*35 Bw4TTC2 , who will undergo ART interruption (ATI) in the context of the ANRS RHIVIERA01 clinical trial.

Overall, this proposal should unveil the phenotype and functional activities of NK cell subsets more relevant to post-treatment control, the influence of early ART initiation and of immunogenetic factors. This information may provide important insight for the development of new immunotherapies aiming HIV remission.