Sherazaan Ismail

The session reviewed recent findings in basic HIV research with the purpose of informing cure strategies. The topics covered were diverse, including identification of novel compounds to enhance latency reversal, describing the interaction of HIV proteins and host RNAs, and characterization of the latent reservoir in children on suppressive ART.

Jacqueline Howard (George Washington University) reported on enhancement of IL-15-mediated latency reversal with the concomitant use of isotretinoin, an FDA-approved retinoid currently used to treat cystic acne. In addition to latency reversal, it also counteracted the pro-survival effects of IL-15. Thus, isotretinoin is a potential new adjunct therapy for “Shock-and-Kill” strategies involving IL-15. Dr. Tinus Schynkel (Ghent University) described the interaction of HIV proteins with host RNAs resulting from the RIP-seq assay. Assessment of these interactions may provide novel insights into host pathways hijacked by HIV for replication, and providing potential novel targets for HIV treatment interventions. Finally, Dr. Marta Massanella (Institut de Recerca de la Sida) presented data on the viral reservoir in Thai children on ART (HIVNAT 209 cohort). Using TILDA, HIV-flow, and mQVOA techniques, they found that the cellular reservoir in children is of a similar composition to that in adults, with the major reservoir detected in central memory cells. They found that cells from children were refractory to stimulation due to undetectable virus by HIV-flow and mQVOA. Furthermore, the reservoir does not become more “inducible” with age as there was no significant difference in the inducibility of HIV after 2.6 years of therapy.

The use of isotretinoin, a clinically relevant compound, shows promise, not just for latency reversal, but also counteracting the pro-survival effects of IL-15, potentiating infected cell death from the cytopathic effects of the virus. The interactome of HIV proteins and host RNA will provide a wealth of data for future mechanistic studies into how HIV hijacks the host cell to persist. Finally, since infant and adult immune systems differ, it is essential to study reservoir composition and dynamics in children to facilitate a cure. Further studies into the mechanisms underlying the refractory nature of reservoir cells in children are needed.