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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.
Wu, Luling; Zheng, Zhihang; Xun, Jingna; Liu, Li; Wang, Jiangrong; Zhang, Xinyu; Shao, Yueming; Shen, Yinzhong; Zhang, Renfang; Zhang, Min; Sun, Meiyan; Qi, Tangkai; Wang, Zhenyan; Xu, Shuibao; Song, Wei; Tang, Yang; Zhao, Bihe; Song, Zichen; Routy, Jean-Pierre; Lu, Hongzhou; Chen, Jun.
Afiliación
  • Wu L; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Zheng Z; Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
  • Xun J; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Liu L; Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.
  • Wang J; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Zhang X; 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.
  • Shao Y; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Shen Y; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Zhang R; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Zhang M; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Sun M; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Qi T; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Wang Z; Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Xu S; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Song W; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Tang Y; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Zhao B; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Song Z; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Routy JP; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Lu H; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  • Chen J; Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Signal Transduct Target Ther ; 9(1): 231, 2024 Sep 09.
Article en En | MEDLINE | ID: mdl-39245675
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzamidas / Infecciones por VIH / VIH-1 / Linfocitos T CD8-positivos / Inhibidores de Histona Desacetilasas / Aminopiridinas Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzamidas / Infecciones por VIH / VIH-1 / Linfocitos T CD8-positivos / Inhibidores de Histona Desacetilasas / Aminopiridinas Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Signal Transduct Target Ther Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido