中药延缓HIV感染者发病的临床研究
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摘要
目前艾滋病公认最有效的治疗方法是高效抗逆转录病毒治疗(Highly activeantiretroviral therapy,HAART)。HAART能有效地抑制艾滋病毒的复制,但却存在着治疗时限、价格昂贵和毒副作用大等的缺点。随着艾滋病治疗研究的开展,中医药治疗艾滋病的优势逐渐显现出来,中药一般毒副作用较小、不易耐药,一旦发现感染即可进行免疫保护治疗,比起HAART更积极主动,对于延缓病情的进展可以起到积极的作用,从卫生经济学的角度看也减少了发病以后的开支。自1987年以来,中国中医科学院广安门医院艾滋病研究室即参与国家中医药管理局坦桑尼亚中医药治疗艾滋病的项目,在中医药治疗艾滋病方面积累了丰富的临床经验,艾灵颗粒就是在本项目10余年实践研究基础上总结出的艾滋病医院中药制剂,具有益气活血解毒作用。本研究采用安慰剂随机对照实验,探讨了中药对HIV早期感染者发病的延缓作用,以便为HIV感染者寻求有效的中医治疗办法。
     1.目的
     本研究通过对HIV早期感染者进行中医药干预治疗,并进行安慰剂随机对照,旨在验证中医药对HIV感染者的疗效及安全性,探讨中医药对HIV感染者发病的延缓作用,从而为HIV感染者提供有效、经济的中药治疗制剂。
     2.方法
     本研究为前瞻性实验研究,采取安慰剂随机对照的实验设计方法,筛选符合纳入标准的HIV感染者90例,分为辨证论治组、艾灵颗粒组和安慰剂对照组,每组病例30例,观察治疗12个月。每月对患者进行一次复诊,观察病情变化,详细记录临床症状体征积分量表,督导服药,并处理临床中出现的问题。分别在治疗的第0、3、6、9、12个月观察患者临床症状体征变化,运用流式细胞技术对CD_4~+T淋巴细胞、CD_8~+T淋巴细胞、CD_3~+T淋巴细胞、CD_4/CD_8、CD_4~+CD_(45)RA表型比例进行检测;在治疗的第0、6、12个月检测患者的病毒载量;在第0、6、12个月时进行安全性指标血常规、尿常规、肝功能、肾功能、心电图、X线的测定。
     3.结果
     患者经观察治疗12个月后,症状体征方面:辨证论治组疗后症状体征总积分明显下降,差异有显著统计学意义(P<0.01);艾灵颗粒组疗后症状体征总积分明显下降,差异有显著的统计学意义(P<0.01);安慰剂对照组症状体征总积分有所下降,但差异无统计学意义(P>0.05)。组间比较:疗后症状体征总积分3组间比较差异有显著统计学意义(P<0.01),结合临床,症状体征总积分改善辨证论治组、艾灵颗粒组均优于安慰剂对照组。卡洛夫斯基积分辨证论治组疗后明显升高,与疗前相比差异有显著统计学意义(P<0.01);艾灵颗粒组疗后卡洛夫斯基积分明显升高,与疗前相比差异有显著的统计学意义(P<0.01);安慰剂对照组疗后卡洛夫斯基积分较疗前有所升高,但差异无统计学意义(P>0.05)。组间比较:疗后卡洛夫斯基积分3组间比较差异有显著统计学意义(P<0.01),结合临床,卡洛夫斯基积分提高辨证论治组、艾灵颗粒组均优于安慰剂对照组。
     免疫指标方面:辨证论治组CD_4~+T淋巴细胞计数治疗后第3、9、12个月和疗前之间差异有显著的统计学意义(P<0.01),治疗后第9、12个月CD_4~+T淋巴细胞计数较疗前明显升高;艾灵颗粒组CD_4~+T淋巴细胞计数治疗后第6个月和疗前之间差异有统计学意义(P<0.05),治疗后第9、12个月CD_4~+T淋巴细胞计数较疗前升高,但差异无统计学意义(P>0.05);安慰剂对照组CD_4~+T淋巴细胞计数治疗后第6个月开始下降,治疗后第9个月和疗前之间差异有统计学意义(P<0.05),治疗12个月和疗前之间差异有显著的统计学意义(P<0.01)。组间比较:辨证论治组、艾灵颗粒组、安慰剂对照组CD_4~+T淋巴细胞计数在治疗后6个月差异有统计学意义(P<0.05),治疗后9、12个月3组间差异有显著的统计学意义(P<0.01),结合临床,辨证论治组、艾灵颗粒组CD_4~+T淋巴细胞计数均较疗前升高,辨证论治组治疗效果优于艾灵颗粒组,安慰剂对照组CD_4~+T淋巴细胞计数较疗前降低。对艾灵颗粒组15例患者CD_4~+CD_(45)RA表型比例分析结果显示,经过治疗后,CD_4~+CD_(45)RA表型所占比例较疗前有增高趋势,各治疗时段与疗前比较无统计学差异(P>0.05)。
     病毒载量方面:辨证论治组治疗各时段病毒载量和疗前相比差异无统计学意义(P>0.05);艾灵颗粒组治疗各时段病毒载量和疗前比较差异也无统计学意义(P>0.05);安慰剂对照组治疗后第12个月时病毒载量明显升高,与疗前比较差异有显著的统计学意义(P<0.01)。组间比较:辨证论治组、艾灵颗粒组、安慰剂对照组病毒载量治疗前后组间无明显统计学差异(P>0.05)。
     安全性指标:治疗过程中患者安全性指标未出现明显的异常改变,也无严重不良反应发生,血尿常规、肝肾功能、心电图、X线治疗前后比较无统计学差异(P>0.05)。
     4.结论
     对HIV早期感染者进行中药干预治疗可以有效地改善患者的临床症状,降低临床症状体征总积分,提高患者的生存质量;还可在一定程度上提高CD_4~+T淋巴细胞计数,提高幼稚CD_4~+T淋巴细胞所占比例,改善机体免疫状况;中药治疗能够使病毒载量维持在相对稳定的水平,可能具有延缓病毒载量升高的潜能;中药治疗HIV感染者毒副作用小,疗效安全,有利于延缓HIV感染者进入发病期的时间。
Highly active antiretroviral therapy(HAART) is currently recognized as the most effective treatment on AIDS.It can effectively suppress the replication of HIV,but it still has some shortcomings such as time limit,expensive and toxic side effects.With the development of AIDS treatment,traditional Chinese medicine(TCM) has gradually appeared its advantages,which has less side effect and resistance.Once it was found to be infected with HIV,TCM can be used to protect the immune function,and the cost is not expensive.
     Since 1987,staffs in department of AIDS research of Guang'an men Hospital,China Academy of Chinese Medical Sciences participated in the project of TCM treatment on AIDS in Tanzania organized by the State Administration of TCM,and accumulated many clinical experiences on TCM treatment of AIDS.Ai-ling granule with the function of strengthening Qi,motivating blood and cleating away toxicity,is a proprietary Chinese medicine preparation which was developed in this project.
     In this study,randomized placebo-controlled experiment on HIV early infected cases is carried out to prove the efficacy and safety of TCM,especially its effect on delaying onset of AIDS,so as to find effective ways of TCM treatment for HIV infected cases.
     1.Objective
     HIV early infected cases are treated with TCM in this randomized placebo-controlled study in order to test the efficacy and safety of TCM,and to explore its effect on delaying onset of AIDS.We hope provide an effective and economic TCM preparation for HIV infected people.
     2.Method
     This is a forward-looking and randomized placebo-controlled study,in which 90 HIV infected cases are intaked and divided into Treatment group,Ai Ling granule group and Placebo control group.30 cases are intaked in each group and observed for 12 months.We visited patients every month.At the 0,3~(rd),6~th,9~(th),12~(th) month we observed their clinical symptoms and tested the count of CD_4~+T lymphocytes,CD_8~+T lymphocytes,CD_3~+T lymphocytes,CD_4/CD_8,and CD_4~+CD_(45)RA;At the 0,6~(th),12~(th) month,we tested the viral load and the safety indicators.
     3.Results
     After 12 months' Observation,results in aspect of signs and symptoms:symptoms in Treatment group and Ai Ling granule group were both developed and the total scores were decreased significantly,there were significant statistical differences(P<0.01);In Placebo control group,total score of symptoms had been reduced to some extend,there was no statistical difference(P>0.05).Comparison among groups:there were significant statistical differences(P<0.01) of symptom total score among the 3 groups after treatment, Treatment group and Ai Ling granule group were better than the Placebo control group. Karnovsky Score in Treatment group and Ai Ling granule group were both significantly increased after treatment,and there were significant statistical differences(P<0.01); Karnovsky Score in the Placebo control group had been increased also,but the difference was not statistically significant(P>0.05).Comparison among groups:there were significant statistical differences(P<0.01) of Karnovsky Score among the 3 groups after treatment,Treatment group and Ai Ling granule group were better than the Placebo control group.
     Results in aspect of immune indicators:there was significant statistical difference (P<0.01) of CD_4~+T lymphocyte count at the 3~(rd),9~(th),12~(th) month in Treatment group,and CD_4~+T lymphocyte count was increased significantly at 9~(th),12~(th) month;There was statistical difference(P<0.01) of CD_4~+T lymphocyte count at the 6~(th) month in Ai Ling granule group(P<0.05),CD_4~+T lymphocyte count was increased at 9~(th),12~(th) month,but there was no statistical difference(P>0.05).CD_4~+T lymphocyte count was decreased from 6~(th) month in the Placebo control group,there was statistical difference at 9~(th) month (P<0.05),and there was significant statistical difference at 12~(th) month(P<0.01). Comparison among groups:there were statistical differences of CD_4~+T lymphocyte count at 6~(th) month among the 3 groups(P<0.05),and significant differences at 9~(th),2~(th) month (P<0.01).CD_4~+T lymphocyte count were both increased in Treatment group and Ai Ling granule group,and Treatment group was better than Ai Ling granule group.CD_4~+T lymphocyte count was decreased in the Placebo control group.CD_4~+CD_(45)RA phenotype ratio analysis of 15 cases in Ai Ling granule revealed the ratio was higher after treatment, though there was no statistical difference(P>0.05).
     Results in aspect of viral load:there were both no statistical differences of viral load in different treatment period of Treatment group and Ai Ling granule group(P>0.05); Viral load in the Placebo control group was significantly increased at 12~(th) month,there was significantly statistical difference(P<0.01).Comparison among groups:there were no statistical differences of viral load among the 3 groups(P>0.05).
     Safety indicators:there were no significant changes in safety indicators,and no serious adverse events(P>0.05).
     4.Conclusion
     The symptoms were developed significantly by intervention of TCM on HIV early infected cases,and the CD_4~+T lymphocyte count and CD_4~+CD_(45)RA phenotype ratio were both improved to some extend.Viral load could be maintained at a relatively stable level, and TCM treatment on HIV infected cases was safe.TCM can delay onset of AIDS.
引文
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    [1]孙利民,危剑安,黄霞珍.从中医理论谈艾滋病的发病机制[J].中华中医药杂志,2005,20(2):100-101
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