Viral and metabolic determinants of HIV-1 reservoir establishment and persistence in ART treated individuals

Defining the mechanisms that determine the size of the viable HIV-1 reservoir will be crucial for the success of HIV-1 eradication strategies.

HIV-1 reservoirs are maintained through cellular longevity or clonal expansion. Since energy metabolism is closely linked to cellular function, quiescent or activated cells have different bioenergetic needs and variable metabolic profiles. Moreover, in HIV-1 infection, the bioenergetic profile of immune cells is a major determinant of their susceptibility to infection and fate. The modulation of immunometabolism as a promising new approach for HIV-1 cure is hampered by paucity of information on determinants of cellular metabolism and how metabolism influences HIV-1 reservoir characteristics and its reactivation potential.

I hypothesise that the immunometabolic profile during acute HIV infection is influenced by transmitted/founder viruses characteristics and these associate with the immune modulatory activity of replication-competent viral reservoirs following suppressive antiretroviral therapy. I will study cellular and plasma metabolic profiles prior to and during treated acute HIV-1 infection, alongside transmitted/founder virus replication capacity and HIV-1 reservoir profiles. These studies will elucidate biological determinants of altered cellular metabolism following HIV-1 infection and how these link to virus and reservoir characteristics. This information may open new strategies for HIV-1 cure or long-term remission.