首页|Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a"shock and kill"strategy for ART-free virological control:a phase Ⅱ single-arm study

Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a"shock and kill"strategy for ART-free virological control:a phase Ⅱ single-arm study

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The combination of ASC22,an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide,a HIV latency reversal agent,may serve as a strategy for antiretroviral therapy-free virological control for HIV.People living with HIV,having achieved virological suppression,were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy.Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+T cells(NCT05129189).15 participants completed the study.At week 8,CA HIV RNA levels showed a significant increase from baseline,and the values returned to baseline after discontinuing ASC22 and chidamide.The total HIV DNA was only transiently increased at week 4(P=0.014).In contrast,integrated HIV DNA did not significantly differ from baseline.Increases in the proportions of effector memory CD4+and CD8+T cells(TEM)were observed from baseline to week 24(P=0.034 and P=0.002,respectively).The combination treatment did not succeed in enhancing the function of HIV Gag/Pol-specific CD8+T cells.Nevertheless,at week 8,a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group(P=0.042 and P=0.034,respectively).Nine adverse events were solicited,all of which were graded 1 and resolved spontaneously.The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs.Further investigations are warranted in the context of analytic treatment interruption.

Luling Wu、Zhihang Zheng、Jingna Xun、Li Liu、Jiangrong Wang、Xinyu Zhang、Yueming Shao、Yinzhong Shen、Renfang Zhang、Min Zhang、Meiyan Sun、Tangkai Qi、Zhenyan Wang、Shuibao Xu、Wei Song、Yang Tang、Bihe Zhao、Zichen Song、Jean-Pierre Routy、Hongzhou Lu、Jun Chen

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Department of Infectious Diseases and Immunology,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China

Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai,China

Shanghai Institute of Infectious Disease and Biosecurity,Fudan University,Shanghai,China

State 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

Department of Clinical Laboratory,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China

Infectious Disease and Immunity in Global Health Program,Research Institute of McGill University Health Centre,Montreal,QC,Canada

Department of Infectious Diseases and Nursing Research Institution,National Clinical Research Center for Infectious Diseases,The Third People's Hospital of Shenzhen,Guangdong,China

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Ascletis Pharma Inc.and the Shanghai Commission of Science and TechnologyAscletis Pharma Inc.and the Shanghai Commission of Science and TechnologyAscletis Pharma Inc.and the Shanghai Commission of Science and Technology

20MC192010020Y3190040021Y11901200

2024

10.1038/s41392-024-01943-9

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

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ISSN：
年,卷(期)：2024.9(10)