BACKGROUND: The combination of chidamide, an HIV latency reversal agent, and an anti-PD-L1 antibody that boosts HIV-specific immunity, has the potential to serve as a “shock and kill” functional cure treatment strategy for HIV.
METHODS: 15 people living with HIV who had achieved virological suppression for at least 1 year were enrolled. Patients received a subcutaneous injection of anti-PD-L1 antibody ASC22 (1mg/kg) once every 4 weeks for a total of 3 times. Chidamide (10 mg) was administered orally twice weekly for 12 weeks while maintaining antiretroviral therapy. Patients were followed up for 24 weeks and changes in the HIV reservoir and HIV-specific CD8+ T cell function were measured (NCT05129189).
RESULTS: Cell-associated (CA) HIV RNA rapidly increased at week 8 and week 12, with mean increases of 4.27 and 3.41-fold (P < 0.001; P=0.017). The combination treatments also resulted in increases in CA HIV RNA to HIV DNA ratios at week 8 and week 12, with mean increases of 1.87 and 2.14-fold from baseline (P=0.001; P=0.008). However, these changes returned to normal at week 24 after discontinuing ASC22 and chidamide. Significant increase in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed at week 24 compared to baseline (P=0.003; P<0.001). Some participants also showed improved function of HIV gag and pol-specific CD8+ T cells and CD8+ TEM cells. 8 adverse events were deemed drug-related, all of which were graded 1 and resolved spontaneously.

CONCLUSIONS: Combination treatment with ASC22 and chidamide for 12 weeks was safe, well-tolerated, which effectively activated latent HIV reservoirs, promoted CD8+ TEM cell proliferation, and had a positive impact on the recovery of HIV-specific CD8+ T cell function. This strategy holds promise for activating and clearing latent HIV reservoirs and deserves further investigation.

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