Figure 5.

Proposed treatment regimen and molecular mechanism of CBL0100. (A) Proposed treatment regimen for the use of CBL0100 in combination with cART for the “block and lock” cure strategy. (1) Acute infection: primary infection of HIV-1 peaks but decreases to stable level when the immune system recognizes the virus (no treatment). (2) Suppressed infection: addition of CBL0100 to cART may intensify cART and lead to faster control of viremia and smaller size of latent reservoirs at the baseline (red line: cART + CBL0100; blue line: cART). (3) Latent infection: addition of CBL0100 and/or other LPAs to cART may prevent the spontaneous viral reactivation (blips) and continue the reduction of reservoir size (red line: cART + CBL0100 and/or other LPAs; blue line: cART). (4) Viral clearance (vs. rebound): addition of CBL0100 and/or other LPAs to cART may eventually reinforce a deep and irreversible silencing of HIV-1 proviruses and lead to the depletion of viral reservoirs for a functional cure (no treatment). (B) Proposed molecular mechanism of CBL100 in suppression of HIV-1 transcription. HIV-1 Tat associates with FACT and recruits it in the proximity to nucleosome at nuc-1. FACT facilites the disassembly and reassembly of the nucleosome at nuc-1 to allow the RNA Pol II to pass for transcriptional elongation. However, in the presence of CBL0100 it intercalates into chromatins and blocks the FACT accessibility/association with nucleosome at nuc-1. RNA Pol II is unable to pass and dissociate from nuc-1. HIV-1 transcription elongation is thus terminated by CBL0100.