Arsenic Trioxide Impacts Viral Latency and Delays Viral Rebound after Termination of ART in Chronically SIV‐Infected Macaques

Advanced Science

Fengyu Hu¹  Linghua Li¹  Weiping Cai¹  Thomas Lehner²  Huachun Zou³  Jin Zhao³  Ruiting Li³  Fengling Feng⁴  Yizi He⁴  Chunxiu Wu⁴  Ling Chen⁴  Fan Zhang⁴  Qing Yang⁴  Enxiang Pan⁴  Pingchao Li⁴  Caijun Sun⁴  Liqiang Feng⁴ 

[1] Guangzhou Eighth People's Hospital Guangzhou Medical University Guangzhou 510182 China;Mucosal Immunology Unit King's College London at Guy's Hospital London WC2R 2LS UK;School of Public Health (Shenzhen) Sun Yat‐sen University Guangdong 518107 China;State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health (GIBH) Chinese Academy of Sciences Guangzhou 510530 China;

关键词: arsenic trioxide;    antiretroviral therapy (ART);    functional cures;    human immunodeficiency virus‐1 (HIV‐1);    latency;    Simian immunodeficiency virus (SIV);   

DOI  :  10.1002/advs.201900319

来源: DOAJ

【 摘 要 】

Abstract The latent viral reservoir is the source of viral rebound after interruption of antiretroviral therapy (ART) and is the major obstacle in eradicating the latent human immunodeficiency virus‐1 (HIV‐1). In this study, arsenic class of mineral, arsenic trioxide, clinically approved for treating acute promyelocytic leukemia, is demonstrated to reactivate latent provirus in CD4+ T cells from HIV‐1 patients and Simian immunodeficiency virus (SIV)‐infected macaques, without significant systemic T cell activation and inflammatory responses. In a proof‐of‐concept study using chronically SIVmac239‐infected macaques, arsenic trioxide combined with ART delays viral rebound after ART termination, reduces the integrated SIV DNA copies in CD4+ T cells, and restores CD4+ T cells counts in vivo. Most importantly, half of arsenic trioxide‐treated macaques show no detectable viral rebound in the plasma for at least 80 days after ART discontinuation. Mechanistically, the study reveals that CD4 receptors and CCR5 co‐receptors of CD4+ T cells are significantly downregulated by arsenic trioxide treatment, which reduces susceptibility to infection after provirus reactivation. Furthermore, an increase in SIV‐specific immune responses after arsenic trioxide treatment may contribute to suppression of viral rebound. This work suggests that arsenic trioxide in combination with ART is a novel regimen in down‐sizing or even eradicating latent HIV‐1 reservoir.

【 授权许可】

Unknown