Michael Roche

In this session, the theme was impacting the reservoir to delay viral rebound. Presentations included: use of an IL-15 superagonist to reactivate HIV reservoirs; the pro-apoptotic drug venetoclax to deplete latently infected cells; allogeneic stem cell transplantation with cells not naturally resistant to HIV; and combination bNAbs with latency reversal.

Jacqueline Howard (George Washington University showed that the cytokine IL-15 could induce the translation-competent HIV reservoir using a novel ultrasensitive assay to detect the viral p24 protein (TRACER assay). Viral reactivation negatively correlated with CD8 T cell counts. Philip Arandjelovic (Walter and Eliza Hall Institute) demonstrated that the Bcl-2 antagonist venetoclax, could deplete latently infected CD4+ T cells in ex vivo culture from people living with HIV and delay viral rebound after cessation of ART in a humanised mouse model of HIV infection. Asier Sáez-Cirión (Institute Pasteur) presented a study where a person living with HIV received an allogeneic stem cell transplantation due to Biphenotypic sarcoma. Unlike other incidences of HIV cure, the donor cells were CCR5 wild type and thus not resistant to HIV. No viral rebound has been observed for 20 months after ceasing ART. Other markers of the HIV reservoir became undetectable as well. Vidisha Singh (Emory University) showed that a cocktail of SIV-targeting antibodies and a potent latency reversal agent could impact the SIV reservoir and rebound dynamics. Reduced levels of SIV DNA in blood and lymph nodes; and lower viral setpoints were observed in Rhesus Macaques that received the SIV-targeting antibodies.

These presentations highlight novel pathways towards achieving ART-free remission. Using pro-apoptotic drugs may target the HIV containing cells that are primed to survive and persist on ART. New latency reversal agents like IL-15 super agonists are more potent than first generation agents and may come with added immune benefits. Data presented here furthers the concept that neutralising antibodies may enhance other aspects of the immune system, the so-called ‘vaccinal effect’. Finally, could demonstration of the absence of viral rebound after stem cell transplantation with CCR5 wild type cells make this a more viable HIV cure option?