Ingenol 3-Hexanoate novel potent reactivator of latent HIV-1.
One of the sgRNAs (LTR5), which binds specifically in the HIV-1 LTR NFκB binding site, was able to promote robust repression of HIV-1 reactivation in latently infected T cells stimulated with Phorbol 12-Myristate 13-Acetate (PMA) and Ingenol B (IngB), both potent protein kinase C (PKC) stimulators._x000D_
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Reference: Retrovirology. 2022 Jun 22;19(1):12. https://pubmed.ncbi.nlm.nih.gov/35733180/
However, significant toxicity risks and the lack of evidence supporting their activity in vivo have limited further evaluation of PKC agonists as HIV latency-reversing agents (LRA) in cure strategies. Here this study evaluated whether GSK445A, a stabilized ingenol-B derivative, can induce HIV/simian immunodeficiency virus (SIV) transcription and virus production in vitro and demonstrate pharmacological activity in nonhuman primates (NHP). In vivo, GSK445A tolerability was established in SIV-na?ve RM at 15 μg/kg although tolerability was reduced in SIV-infected RM on ART. 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._x000D_
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Reference: PLoS Pathog. 2022 Jan 18;18(1):e1010245. https://pubmed.ncbi.nlm.nih.gov/35041707/
Ingenol 3-Hexanoate, or Ingenol B, is a novel potent reactivator of latent HIV-1.
