(5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART : a randomized, double-blinded, placebo-controlled phase II study
© 2023 The Authors..
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/mm3, comparable among three groups. LLDT-8 was well-tolerated in all participants. At 48 weeks, change of CD4 counts was 49 cells/mm3 in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm3 in HT8 group (95% CI: 41, 85), compared to 32 cells/mm3 in placebo group (95% CI: 13, 51). LLDT-8 1 mg daily significantly increased CD4 count compared to placebo (p = 0.036), especially in participants over 45 years. The mean change of serum interferon-γ-induced protein 10 was -72.1 mg/L (95% CI -97.7, -46.5) in HT8 group at 48 weeks, markedly decreased compared to -22.8 mg/L (95% CI -47.1, 1.5, p = 0.007) in placebo group. Treatment-emergent adverse events (TEAEs) were reported in 41 of 46 (89.1%) participants in HT8 group, 43 of 51 (84.3%) in LT8, and 42 of 52 (80.7%) in PL group. No drug-related SAEs were reported.
Interpretation: LLDT-8 enhanced CD4 recovery and alleviated inflammation in long-term suppressed INRs, providing them a potential therapeutic option.
Fundings: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Shanghai Pharmaceuticals Holding Co., Ltd., and the National key technologies R&D program for the 13th five-year plan.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
The Lancet regional health. Western Pacific - 34(2023) vom: 11. Mai, Seite 100724 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Wei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 08.06.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT04084444 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.lanwpc.2023.100724 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357858387 |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT04084444 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 The Authors. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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/mm3, comparable among three groups. LLDT-8 was well-tolerated in all participants. At 48 weeks, change of CD4 counts was 49 cells/mm3 in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm3 in HT8 group (95% CI: 41, 85), compared to 32 cells/mm3 in placebo group (95% CI: 13, 51). LLDT-8 1 mg daily significantly increased CD4 count compared to placebo (p = 0.036), especially in participants over 45 years. The mean change of serum interferon-γ-induced protein 10 was -72.1 mg/L (95% CI -97.7, -46.5) in HT8 group at 48 weeks, markedly decreased compared to -22.8 mg/L (95% CI -47.1, 1.5, p = 0.007) in placebo group. Treatment-emergent adverse events (TEAEs) were reported in 41 of 46 (89.1%) participants in HT8 group, 43 of 51 (84.3%) in LT8, and 42 of 52 (80.7%) in PL group. No drug-related SAEs were reported | ||
| 520 | |a Interpretation: LLDT-8 enhanced CD4 recovery and alleviated inflammation in long-term suppressed INRs, providing them a potential therapeutic option | ||
| 520 | |a Fundings: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Shanghai Pharmaceuticals Holding Co., Ltd., and the National key technologies R&D program for the 13th five-year plan | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Song, Xiaojing |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Lianfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lijun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, An |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hongxin |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Hongxia |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Biao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Liying |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Ting |e verfasserin |4 aut | |
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| 700 | 1 | |a Zuo, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Taisheng |e verfasserin |4 aut | |
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