Hello everyone, I’m Xiaosheng Liu , a graduate student from Professor Taisheng Li’s team of Peking Union Medical College Hospital, China. My primary research focus is on the mechanisms underlying immunological non-response in HIV/AIDS patients after long-term antiviral therapy and the development of therapeutic drugs for this condition. I’m delighted to participate in this year’s APACC conference (2023) and present two poster studies conducted by our team at the conference. APACC is the most cutting-edge and top academic conference in the Asia-Pacific region for HIV/AIDS, and I hope to broaden my knowledge in various aspects through this conference.
As we all know, immunological non-response in HIV/AIDS patients is a challenging problem that needs to be addressed urgently in the field. Over the past few decades, various drugs, such as interleukin-2 and chloroquine, have been attempted to improve immunological non-response in HIV/AIDS patients, but clinical trials have consistently ended in failure. To date, effective treatment options for this subset of HIV/AIDS patients with immunological non-response remain scarce.
Over the years, our team, under the leadership of Professor Li, has conducted in-depth research into the mechanisms of immunological non-response resulting from chronic inflammation. At this year’s APACC conference, we presented two research studies conducted by our team. One of them is a study on a novel drug treatment for immunological non-responders, where we conducted a nationwide multicenter phase II clinical trial of (5R)-5-hydroxytriptolide for the treatment of immunological non-response in HIV/AIDS patients. Nine centers across the country participated in this study, which was conducted in strict accordance with international standards, including prospective, randomized, double-blind, and double-simulation design. The results showed that after 48 weeks of treatment with 1 mg of (5R)-5-hydroxytriptolide once daily, there was a significant increase in peripheral blood CD4+ T-cell counts in HIV/AIDS patients with immunological non-response (63/mm3), which was significantly higher than the placebo group and the low-dose 0.5 mg group. The study also demonstrated a more pronounced increase in peripheral blood CD4+ T-cell counts, reaching 96/mm3, in patients aged 45 and above. Additionally, (5R)-5-hydroxytriptolide significantly reduced the level of inflammation in HIV/AIDS patients, with a similar rate of adverse reactions among different groups.
In another study, we used rhesus macaques infected with simian immunodeficiency virus (SIV) to model HIV infection and applied (5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase II study. The results showed that (5R)-5-hydroxytriptolide treatment significantly inhibited the expression of activating genes in SIV-infected rhesus macaques. Furthermore, this finding was validated at the level of peripheral blood mononuclear cells (PBMCs) in humans.
Overall, from preclinical research to clinical trials, we have explored the potential of (5R)-5-hydroxytriptolide in treating immunological non-response in HIV/AIDS patients. As of now, (5R)-5-hydroxytriptolide is the only drug shown to be helpful in improving immunological non-response in HIV/AIDS patients through rigorous clinical trials, which is of significant importance to HIV/AIDS research and clinical practice.
Regarding (5R)-5-hydroxytriptolide, it is derived from the active ingredient triptolide in Tripterygium wilfordii Hook F, and previous studies have shown that Tripterygium wilfordii Hook F has immunomodulatory and anti-inflammatory effects and has long been used in traditional Chinese medicine to treat rheumatic immune diseases and other conditions. (5R)-5-hydroxytriptolide retains the effectiveness of Tripterygium wilfordii Hook F while significantly reducing its toxicity, resulting in a class I new chemical drug with independent intellectual property rights. Currently, (5R)-5-hydroxytriptolide is also undergoing clinical research for the treatment of rheumatoid arthritis. We look forward to seeing more significant therapeutic effects in future phase III clinical trials.
Original Article Link:
Cao W, Liu X, Han Y, Song X, Lu L, Li X, et al. (5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase II study. Lancet Reg Health West Pac. 2023 Mar 15;34:100724. doi: 10.1016/j.lanwpc.2023.100724.
