(5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase II study

作者：Wei Cao, Xiaosheng Liu, Yang Han, Xiaojing Song, Lianfeng Lu, Xiaodi Li, Ling Lin, Lijun Sun, An Liu, Hongxin Zhao, Ning Han, Hongxia Wei, Jian Cheng, Biao Zhu, Min Wang, Ying Li, Ping Ma, Liying Gao, Xicheng Wang, Jianhua Yu, Ting Zhu, Jean‐Pierre Routy, Min Zuo, Taisheng Li · 发表于：The Lancet Regional Health - Western Pacific · 年份：2023 · DOI：10.1016/j.lanwpc.2023.100724 · 被引用次数：23 · 研究领域：Natural Compounds in Disease Treatment、Autoimmune and Inflammatory Disorders Research、Andrographolide Research and Applications

Background Therapeutic approaches to HIV-suppressed immunological non-responders (INRs) remain unsettled. We previously reported efficacy of Chinese herbal Tripterygium wilfordii Hook F in INRs. Its derivative (5R)-5-hydroxytriptolide (LLDT-8) on CD4 T cell recovery was assessed. Methods The phase II, double-blind, randomized, placebo-controlled trial was conducted in adults patients with long-term suppressed HIV infection and suboptimal CD4 recovery, at nine hospitals in China. The patients were 1:1:1 assigned to receive oral LLDT-8 0.5 mg or 1 mg daily, or placebo combined with antiretroviral therapy for 48 weeks. All study staff and participants were masked. The primary endpoints include change of CD4 T cell counts and inflammatory markers at week 48. This study is registered on ClinicalTrials.gov (NCT04084444) and Chinese Clinical Trial Register (CTR20191397). Findings A total of 149 patients were enrolled from Aug 30, 2019 and randomly allocated to receiving LLDT-8 0.5 mg daily (LT8, n = 51), 1 mg daily (HT8, n = 46), or placebo (PL, n = 52). The median baseline CD4 count was 248 cells/mm 3 , comparable among three groups. LLDT-8 was well-tolerated in all participants. At 48 weeks, change of CD4 counts was 49 cells/mm 3 in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm 3 in HT8 group (95% CI: 41, 85), compared to 32 cells/mm 3 in placebo group (95% CI: 13, 51). LLDT-8 1 mg daily significantly increased CD4 count compared to placebo (p = 0.036), especially ...