Retrovirus, Infection and Latency
My research is focusing on HIV and SIV reservoir characterization at the molecular, cellular and tissue levels for more than 15 years. For example I have a particular interest in the different subsets of CD4+ T cells and in reservoirs in tissues (such as the rectum, kidney grafts, and adipose tissue…). More recently P-VISCONTI study from the RHIVIERA consortium (experimental model of macaque infection) permits to consider viral reservoirs and their dynamics more largely in the organism.
I am involved in collaborative studies of patients at the time of primary infection, as well as long-term non progressors and posttreatment controllers. I participated in the description of this remission status and I am taking part in the characterization of this peculiar control of infection after treatment interruption. I am also the virologic investigator in several clinical trials of early antiretroviral treatment and personalized medicine (deescalation strategies…) and develop ancillary studies on HIV reservoirs in these trials. I am participating in different programs, most of them developed within the framework of the consortium RHIVIERA: ANRS iVISCONTI : international Viro-Immunologic Sustained CONtrol after Treatment Interruption ; ANRS CODEX cohort HIV controllers, P-VISCONTI: A non-human primate model for HIV remission ; ANRS RHIVIERA 01 trial: Assessment of HIV remission upon cART interruption in early treated individuals from ANRS CO6 PRIMO cohort carrying the MHC genotype B35(53) Bw4TTC2 ; ANRS RHIVIERA 02 trial: a randomized multicentric control trial testing the impact on post-treatment HIV control of dual long-acting HIV-specific broadly neutralizing antibodies; in combination with Dolutegravir + Emtricitabine + Tenofovir in HIV infected individuals undergoing primary HIV-1 infection.
I am interested in continuing to participate in programs to understand the mechanisms underlying control of infection without treatment, to search for biomarkers predictive of a durable remission and to evaluate new strategies for HIV/SIV cure (pathophysiological studies, preclinical and clinical trials).
In my group, we developed different tools for the characterization of HIV/SIV reservoirs:
- quantification of viral reservoirs (total and integrated HIV DNA, SIV DNA), of the transcriptional activity of reservoir (cell-associated HIV-RNA, cell-associated SIV-RNA), quantification of residual viremia and production of HIV/SIV RNA after cell simulation ex vivo, with ultrasensitive assays. These assays have been validated in cell lines, humans, macaques and humanized mice,
- tools based on next-generation sequencing (amplicon strategies, Illumina and Nanopore) for studying the distribution and dynamics of the quasispecies in the organism (HIV and SIV assays with phylogenetic approaches),
- tools based on next-generation sequencing for the characterization of integrated HIV DNA (near full-length genome) to determine the proportion and quantity of intact proviruses and the genetic defects of other proviruses.
- ddPCR for quantification of intact proviruses (HIV and SIV).
We are continuing to develop other tools in this objective based on recent technologies for HIV and SIV.
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