针对 HIV 和肝病的虚拟 CROI 2022 总结 2030 年消除肝炎是否顺利

StephenW

针对 HIV 和肝病的虚拟 CROI 2022 总结
2030 年消除肝炎是否顺利？
脂肪肝疾病是一个日益严重的问题吗？
CROI 2022 的新见解。


  Jurgen K. Rockstroh 医学博士，医学教授
德国波恩大学

一致：
Jurgen K. Rockstroh 博士教授
医学部
波恩大学医院
Venusberg-校园 1
53127 波恩
德国

提炼：
“总体而言，几乎没有任何关于新型 HBV 治疗药物的数据。但值得注意的是，一项动物研究报告了一种纳米制剂替诺福韦 (TFV) 前药，该药物能够在单次治疗后三个月内抑制人源化和转基因小鼠的 HBV DNA。肌肉注射 (6). 在本研究中，合成了一种亲脂性 TFV 前药 M1TFV，并通过高压均化将其纳米配制成稳定的泊洛沙姆 407 稳定的水性纳米晶体 (NM1TFV)。制备 TAF 的固体药物纳米晶体 (NTAF) 并用作对照。在单次肌肉注射 168 mg/kg TFV 等效物 NM1TFV 或 NTAF 后，在两种小鼠模型（HBV 感染的人源化肝 TK-NOG 小鼠和 HBV 转基因 Tg05 小鼠）中评估制剂功效。评估外周血中的 HBV DNA 水平每两周一次，为期 12 周。在 TK-NOG 小鼠的染色肝切片上评估 HBV 标志物 HBcAg 和 HBsAg。通过质谱法定量药物水平。向感染HBV的人源化TK-NOG小鼠肌肉注射NM1TFV可抑制外周血和肝脏中的病毒DNA达三个月。在 NM1TFV 治疗的小鼠中，HBcAg 和 HBsAg 水平在三个月内同样受到抑制。总体而言，NM1TFV 制剂耐受性良好，在注射部位未观察到肌肉退化、嗜碱性粒细胞或嗜酸性粒细胞浸润、蜂窝织炎或脓肿的证据。作者得出结论，NM1TFV 可以开发为慢性 HBV 感染的治疗方法。就像在其他医学领域一样，长效治疗方案的开发可能会引起 HBV 患者的极大兴趣，这些患者可能需要终生治疗慢性 HBV 感染并面临依从性挑战。 "

StephenW

Summary from virtual CROI 2022 for HIV and liver disease
Hepatitis elimination for 2030 on track?
Is fatty liver disease a growing concern?
New insights from CROI 2022.


          Jurgen K. Rockstroh M.D., Professor of Medicine
University of Bonn, Germany

Correspondence:
Prof. Dr. Jurgen K. Rockstroh
Department of Medicine I
University Hospital Bonn
Venusberg-Campus 1
53127 Bonn
Germany

Extract:
"Overall, hardly any data was presented on new HBV treatment agents. Of note, however was an animal study which reported on a nanoformulated tenofovir (TFV) prodrug which was able to suppress HBV DNA in humanized and transgenic mice for three months following a single intramuscular injection (6). For this study a lipophilic TFV prodrug, M1TFV, was synthesized and nanoformulated into stable poloxamer 407 stabilized aqueous nanocrystals (NM1TFV) by high pressure homogenization. Solid drug nanocrystals of TAF (NTAF) were produced and used as controls. Formulation efficacy was evaluated in two mouse models (HBV-infected humanized liver TK-NOG mice and HBV transgenic Tg05 mice) following a single intramuscular injection of 168 mg/kg TFV equivalents of either NM1TFV or NTAF. HBV DNA levels in peripheral blood were assessed biweekly for 12 weeks. HBV markers HBcAg and HBsAg were evaluated on stained liver sections of TK-NOG mice. Drug levels were quantified by mass spectrometry. A single intramuscular injection of NM1TFV to HBV infected humanized TK-NOG mice suppressed viral DNA in peripheral blood and liver for three months. Levels of HBcAg and HBsAg were equally suppressed over three months in NM1TFV treated mice. Overall, NM1TFV formulations were well tolerated and no evidence of muscle degeneration, basophil or eosinophil infiltration, cellulitis or abscesses were observed at the injection site. The authors conclude that NM1TFV can be developed as a therapy for chronic HBV infection. Just as in other medical areas development of long-acting treatment options could be of considerable interest in HBV patients who require potentially lifelong treatment of chronic HBV infection and are facing adherence challenges. "

StephenW

https://natap.org/2022/CROI/croi_182.htm

pppq123

但值得注意的是，一项动物研究报告了一种纳米制剂替诺福韦 (TFV) 前药，该药物能够在单次治疗后三个月内抑制人源化和转基因小鼠的 HBV DNA
这段话有点意思。
但愿早日在人的身上试验成功。

newchinabok

pppq123 发表于 2022-9-18 22:29
但值得注意的是，一项动物研究报告了一种纳米制剂替诺福韦 (TFV) 前药，该药物能够在单次治疗后三个月内抑 ...

慢慢去做梦，拉些战友一起做梦

tim889

pppq123 发表于 2022-9-18 06:29
但值得注意的是，一项动物研究报告了一种纳米制剂替诺福韦 (TFV) 前药，该药物能够在单次治疗后三个月内抑 ...

老鼠里都没有cccDNA，这种模型如果用来研究functional cure，看看笑笑就好了

StephenW

tim889 发表于 2022-9-19 12:01
老鼠里都没有cccDNA，这种模型如果用来研究functional cure，看看笑笑就好了

"老鼠里都没有cccDNA，"  - 不正确和过时!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933441/
Front Immunol. 2021; 12: 638447.
Published online 2021 Feb 19. doi: 10.3389/fimmu.2021.638447
PMCID: PMC7933441
PMID: 33679796
Establishment of Humanized Mice for the Study of HBV
Fritz Lai,1,2,* Cherry Yong Yi Wee,1 and Qingfeng Chen1,3,4,*

"It was only until recently when recombinant HBV cccDNA was successfully generated in mice injected hydrodynamically through Cre-/Loxp-mediated recombination which functions similarly to real HBV cccDNA in the production of mature viruses (14, 25). More importantly, the improved stability and persistence of HBV severely damaged mice livers for the very first time which resulted in advanced liver pathogenesis evidenced by development of fibrosis (26). Although transgenic mice exhibiting such phenotype was considered a major breakthrough in the field of HBV in vivo, the study still revolved around a complete mouse host setting. Since human hepatocytes are the natural cellular target of HBV, the inevitable transition of mouse to human eventually gave rise to various establishments of human liver chimeric mice."

上述评论提到了“长效治疗方案” (long-acting treatment), 与功能性治愈无关.

newchinabok

tim889 发表于 2022-9-19 12:01
老鼠里都没有cccDNA，这种模型如果用来研究functional cure，看看笑笑就好了

tim先生，你的DNA没转阴吗？上海长海医院万谟斌有二片恩替和恩替+taf
方案，转阴后撤一片恩替，单药。好大夫图文问答挂他号，他回答很及时，态度好，和有耐心，你可以研究研究，问问

newchinabok

万谟彬:部分病毒学应答，需要调整用药方案或联合治疗。当联合治疗得到病毒学完全应答、病毒检测在20IU/ml以下后，再改成单药治疗。如恩替卡韦联合丙酚替诺福韦，达到完全病毒学应答达后，可停掉恩替卡韦，以丙酚替诺福韦维持治疗

newchinabok

二片恩替也有方案