IPI-443 / Infinity Pharma - LARVOL DELTA

Synergistic effects of romidepsin with PI3K inhibitors in reducing the pool of HIV latently infected cells ex vivo (IAS-HIV 2023) - " We assessed the effects of three different PI3K inhibitors (IPI-443, IPI-3063 and wortmannin) alone and in combination with LRAs (romidepsin, panobinostat, JQ1 and PMA/PHA as a positive control) to determine if these pro-apoptotic agents enhanced death of HIV-infected cells using CD4+ T-cells isolated from blood from n=6 PLWH on ART. Taken together, the data suggests that sensitisation of latently infected CD4+ T-cells with pro-apoptotic compounds combined with latency reversal to drive expression of viral pro-apoptotic proteins can enhance the clearance of latently infected cells. The combination of romidepsin and select PI3K inhibitors could inhibit multiple cell survival pathways, ultimately leading to the production of ROS and an increase in pro-apoptotic molecules."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • CD4

[VIRTUAL] ROMIDEPSIN COMBINED WITH PRO-APOPTOTIC DRUGS REDUCE INTEGRATED HIV DNA (CROI 2020) - "CD4+ T-cells were treated with pro-apoptotic drugs (the phoshoinositide-3 kinase (PI3K) inhibitors, IPI-443, IPI-3063 and wortmannin or an inhibitor of B-cell lymphoma (Bcl)-2, venetoclax) for 24 hours, followed by treatment with five different latency reversing agents (LRAs; panobinostat, romidepsin, bryostatin, JQ1 or PMA/PHA) for 4 or 24 hours and then the pro-apoptotic drugs alone for a further 48 hours. Using CD4+ T-cells from PLWH on ART ex vivo, reduction of integrated HIV DNA could be significantly enhanced using the combination of romidepsin with either a PI3K or Bcl-2 inhibitor. The addition of a pro-apoptotic drug could potentially provide the kill needed for effective shock and kill."

IO Biomarker