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

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Qing Yang, Fengling Feng, Pingchao Li, Enxiang Pan, Chunxiu Wu, Yizi He, Fan Zhang, Jin Zhao, Ruiting Li, Liqiang Feng, Fengyu Hu, Linghua Li, Huachun Zou, Weiping Cai, Thomas Lehner, Caijun Sun, Ling Chen

Original languageEnglish
Article number1900319
Pages (from-to)3-10
JournalAdvanced Science
Volume6
Issue number13
Early online date7 May 2019
DOIs
Publication statusPublished - 3 Jul 2019

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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 termina-tion, 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 recep-tors and CCR5 co-receptors of CD4+ T cells are significantly downregulated by arsenic trioxide treatment, which reduces susceptibility to infection after pro-virus 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.

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