Figure 4.

Inhibition of anti-apoptotic proteins reverses HIV latency. Debio 1143 (an IAP inhibitor) inhibits anti-apoptotic proteins such as BIRC2, which activates NF-κB-mediated HIV reversal. HIV latency can be markedly reversed in ART-treated BLT mice and human subjects when treated with Debio 1143. On the other hand, Debio 1143, when combined with anti-PD1 monoclonal antibody (mAb), can reduce HIV production and latency reversion in BLT humanized mice in most tissues (spleen, lymph nodes, liver, lungs, and thymic organoids). The dual role of chemical agents in HIV reversal/maintenance is thus intriguing and warrants further investigation.