Title

A randomized controlled trial of (5R)-5-hydroxytriptolide in HIV INRs receiving ART

Presenter

Wei Cao

Authors

W. Cao¹, X. Liu², Y. Han¹, X. Song¹, L. Lu¹, X. Li¹, J.-P. Routy³, M. Zuo⁴, T. Li^1,2

Institutions

¹Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Department of Infectious Diseases, Beijing, China, ²Tsinghua University, School of Medicine, Beijing, China, ³McGill University Health Centre, Montreal, Canada, ⁴Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai, China

BACKGROUND: Therapeutic approaches to HIV-suppressed immunological non-responders (INRs) remain unsettled. We previously reported the 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 adult patients with long-term suppressed HIV infection and suboptimal CD4 recovery, at eight hospitals in China. The patients were 1:1:1 assigned to receive oral LLDT-8 0·5mg or 1mg 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).
RESULTS: A total of 149 patients were enrolled from Aug 30, 2019, and randomly allocated to receiving LLDT-8 0·5mg daily (LT8, n= 51), 1mg daily (HT8, n= 46), or placebo (PL, n= 52). The median baseline CD4⁺ T cell count was 248 cells/mm³, comparable among three groups. LLDT-8 was well tolerated in all participants. At 48 weeks, change of CD4⁺ T cell counts was 49 cells/mm³ in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm³ in the HT8 group (95% CI: 41, 85), compared to 32 cells/mm³ in the placebo group (95% CI: 13, 51). LLDT-8 1mg daily significantly increased CD4⁺ T cell count compared to placebo (P=0·036), especially in participants over 45 years old. The mean change of serum interferon-?-induced protein 10 (IP-10) was -72·1 mg/L (95% CI -97·7, -46·5) in the HT8 group at 48 weeks, markedly decreased compared to -22·8 mg/L (95% CI -47·1, 1·5, P=0·007) in the placebo group. Treatment-emergent adverse events (TEAEs) were reported in 41 of 46 (89·1%) participants in the HT8 group, 43 of 51(84·3%) in LT8, and 42 of 52 (80·7%) in the PL group. No drug-related serious adverse events (SAEs) were reported.
CONCLUSIONS: LLDT-8 enhanced CD4 recovery and alleviated inflammation in long-term suppressed INRs, providing them a potential therapeutic option.

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