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Title
Anti-PD-L1 antibody ASC22 in combination with chidamide potentiates HIV latency reversal and immune function from ART-suppressed individuals: a single center, single-arm, phase 2 study
Presenter
Luling Wu
Authors
L. Wu1,2, Z. Zheng1,3, J. Xun1,4, L. Liu1, J. Wang1, R. Zhang1, M. Sun1, H. Lu5, J. Chen1
Institutions
1Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China, 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China, 3Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China, 4State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China, 5Department of Infectious Diseases and Nursing Research Institution, National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen, Shenzhen, China

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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