ingenol-B stabilized (GSK445A) / GSK - LARVOL DELTA

Different Impact of Latency Reversal in Cells From People With HIV Viremia and With ART Suppression (CROI 2024) - "Here, we compared the effect of the ingenol-based PKC agonist GSK445A alone or in combination with the HDACi romidepsin (RMD) on HIV transcription in cells from viremic and virally suppressed individuals.We measured the effect GSK445A +/- RMD on HIV transcription in CD4+ T cells isolated from the blood of 10 PWH on ART with undetectable plasma viral load as well as in 18 untreated individuals (median = 3.31×10^5 HIV RNA copies/mL). The combination of GSK445A and RMD leads to an apparent reduction in the levels of HIV transcripts in cells isolated from viremic PWH. This decrease is abrogated by a caspase inhibitor, suggesting that latency reversal in a viremic setting leads to the death of the infected cells. Our results suggest that the administration of LRAs at the time of ART initiation, when the bulk of the reservoir is established, may reduce the frequency of persistently infected cells."

Human Immunodeficiency Virus • Infectious Disease • CD4

The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription. (PubMed, PLoS Pathog) - "Increases in plasma viremia following GSK445A administration were suggestive of increased SIV transcription in vivo. Collectively, these results indicate that GSK445A is a potent HIV/SIV LRA in vitro and has a tolerable safety profile amenable for further evaluation in vivo in NHP models of HIV cure/remission."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • CD8 • IFNG