广西常用的2个治疗艾滋病中药对HIV耐药性和抗病毒药疗效的影响

Shenlingfuzheng Capsule and Qingdu Capsule are two locally developed preparations of traditional Chinese medicine (TCM) used for patients with HIV/AIDS. Since these two preparations are found to ameliorate the symptoms of HIV/AIDS patients, and to reduce and relieve the side effects of antiretroviral agents, they have been used as the major adjvants for AIDS patients in Guangxi. However, some clinicians are concerned that TCM preparations may reduce the side effects of antiretroviral agents by lowering the blood concentrations of antiretroviral agents, which may also compromise the potency of antiretroviral agents, and even contribute to HIV drug resistance. The aim of the present project is to demonstrate the impacts of these two TCM preparations on HIV drug resstance and the effect of antiretroviral agents through an animal experiment, a cross-sectional study, and a clinical experiment. An animal experiment on rats will be conducted to investigate the effect of these two TCM preparations on pharmacokinetics of the first-line antiretroviral regimens. In the cross-sectional study, HIV/AIDS patients are about to be surveyed, and the relationship between TCM preparations and HIV drug resistance, and that between TCM preparations and virological or immuological responses are to be analyzed. The influencing factors related to these relationships are also to be explored in the cross-sectional study. The clinical experiment is designed by referring to the results of the above study, and HIV/AIDS patients who do not ever receive HAART, Shenlingfuzheng Capsule,or Qingdu Capsule are to be recruited in this study. Then, the differences of HIV drug resistant mutations and the clinical effects are to be observed after one year of treatment with three regimens: antiretroviral agents, a combination of HAART and Shenlingfuzheng Capsule, and a combination of antiretroviral agents and Qingdu Capsule. The findings of this study may be directly applied in clinical practice, and may provide guidance for the optimization of treatment plans with a combination of TCM and antiretroviral agents for HIV/AIDS patients.

参灵扶正胶囊和清毒胶囊是广西自主研发的、用于治疗艾滋病的中成药。它们因可以改善艾滋病患者的某些症状、减少或减轻抗病毒药的毒副作用而成为当地主要的艾滋病辅助用药。在临床工作中，有人担心中药可能通过降低抗病毒药的血药浓度而降低其毒副作用，并可能因此降低抗病毒疗效甚至导致耐药。为此，本项目通过动物实验、横断面研究和临床实验探讨2中药对HIV耐药性和抗病毒疗效的影响。动物实验以大鼠为研究对象，观察中药对一线抗病毒药药代动力学的影响；横断面研究以艾滋病感染者和病人为研究对象，探讨中药与HIV耐药性和患者的病毒学应答、免疫学应答之间的关联及其可能的影响因素；临床研究在参考以上研究结果的基础上设计研究方案，以初治患者为研究对象，观察抗病毒药、抗病毒药+参灵扶正胶囊、抗病毒药+清毒胶囊3种方案治疗1年后HIV耐药性突变和抗病毒疗效的差异。本研究成果将直接应用于临床，为优化艾滋病中西医结合治疗方案提供指导。

项目的背景：参灵扶正胶囊和清毒胶囊可以改善艾滋病患者的某些症状、减少或减轻抗病毒药的毒副作用而成为当地主要的艾滋病辅助用药。在临床工作中，有人担心中药可能通过降低抗病毒药的血药浓度而降低其毒副作用，并可能因此降低抗病毒疗效甚至导致耐药。.主要研究内容：本项目通过动物实验、横断面研究和临床实验探讨2中药对HIV耐药性和抗病毒疗效的影响。动物实验以大鼠为研究对象，观察中药对一线抗病毒药药代动力学的影响；横断面研究以艾滋病感染者和病人为研究对象，探讨中药与HIV耐药性和患者的病毒学应答、免疫学应答之间的关联及其可能的影响因素；临床研究以初治患者为研究对象，观察抗病毒药、抗病毒药+参灵扶正胶囊、抗病毒药+清毒胶囊3种方案治疗1年后HIV耐药性突变和抗病毒疗效的差异。.重要结果及关键数据：.1.在大鼠动物实验中，清毒胶囊和参灵扶正胶囊对AZT、3TC和EFV的各项药动学参数无明显影响，仅见AZT的t1/2的改变，提示2个中药可能加快了AZT的代谢，但结合其他参数（如AUC0-12h、Cmax）进行分析，它们对AZT血药浓度及代谢的影响较小。.2. 在横断面调查研究中，我们对比了接受HAART、HAART联合参灵扶正胶囊和HAART联合清毒胶囊治疗艾滋病患者的HIV RNA、T淋巴细胞亚群和HIV耐药性突变，结果HIV RNA<100拷贝/ｍl者分别占91.76%、83.52%和86.55%；HIV RNA 100～1000拷贝/ｍl者分别占4.12％、7.95％和4.68％；HIV RNA>1000拷贝/ｍl者分别占4.12％、8.52％和8.77％；3组CD4细胞计数分别为370.68±1.77、345.60±1.71和327.67±1.85个／μL；耐药性突变发生率分别为１.18％、３.41％和４.68％。.3. 在临床研究中，分别用HAART、HAART联合参灵扶正胶囊或清毒胶囊治疗艾滋病患者，1年后，CD4计数分别增加165.0、178.0 和145.0 个/µl；A组 94% 、B组96%、C组 92%的患者HIV RNA 低于最低检测限；14个不良反应中，仅乏力和头晕组间差异有统计学意义(P<0.05)；CD4计数增加数、HIV RNA和耐药性突变率均无统计学意义。.科学意义：2中药对HAART药代动力学、疗效和HIV耐药性未产生不利影响，但其临床效果也不甚显著。