Study On Therapeutic Effect And Mechanism Of HIV/AIDS By Treatment With Traditional Chinese Medicine Compound KA

Background:AIDS(Acquired immunodeficiency syndrome)is caused by the HIV(Human Immunodeficiency Virus)which could destroy the human’s immune system.Nowadays,AIDS epidemic and harm has spread to 194 countries and regions in the world.Although scientists has developed lots of drug and treatment for HIV/AIDS,but the limitations still exists such as ADR,drug resistance etc.The target of the new treatment strategies combined medicine with traditional Chinese medicine(TCM)is to improve the immunological function of patients and to enhance the live quality of patients,and more importantly,to further bring into play the superiority of TCM clinically during the treatment.In order to provide theoretical basis and application foundation of the KA preparation,this paper has studied the HIV/AIDS clinical treatment characteristics with the application of a long-term TCM compound preparation and has investigated the therapeutic effect and mechanism from the perspective of cellular immunity and viral regulator genes expression.Part Ⅰ:Retrospective study of therapeutic effect of HIV/AIDS by treatment with KAObjective:A retrospective cohort study were applied to evaluate the therapeutic effect of HIV/AIDS by treatment with KA(traditional Chinese medicine compound)Methods:Information of 132 HIV/AIDS patients coming from Yunnan provinces and treated with KA in the year 2004-2011 was collected.Comparisons were performed to the changes of the indexes(CD4+T cells,CD8+T cells,blood biochemical parameters,symptom score,live quality e.c.t)of different baseline CD4+T cells during 36 months.The incidence rate of effectivity,recovery and abnormal were computed.The factors related to the retention,efficacy and recovery rates in the treatment of HIV/AIDS with KA were analysised by stepwise regression.Results:(1)During 36 months of HIV/AIDS patients treated with KA follow-up,Compare with 0 month,the midian CD4+T lymphocyte counts add 126 cells/μl at 36 month,increased by with average annual rate of about 42 cells/μl.It is showed a statistically increased among patients with baseline CD4+T cells<350 cells/μl.CD4+T lymphocyte counts median maintain stable among patients with baseline CD4+T≥350 cells/μl.(2)During 36 months of HIV/AIDS patients treated with KA follow-up,The percentage of CD4+T lymphocyte count recovered to more than 500 cells/μl was 43.59%.There was a significant difference between different group by baseline CD4+T cells.Patients with baselin≥350 CD4+T were statistically higher.(3)During 36 months of HIV/AIDS patients treated with KA follow-up,compare with 0 month,the patient’s symptoms total score was significantly decreased(P<0.05),Kamovsky Score significantly increased(P<0.05).And during the medication 3 to 6 months showed the most obvious,and then go to the plateau.Compared with 0 months,the scores of symptoms inculuding physical disease,fever,cough,fatigue,poor appetite,shortness of breath,spontaneous sweating,night sweats,itching skin was decreased significantly.(P<0.05).(4)During 36 months of HIV/AIDS patients treated with KA follow-up,the abnormal percentages of blood biochemical indicators overall downward trend.The median for each index statistics show,WBC、LY、ALT、AST stabilize,PLT、HB、CR、BUN increased after treatment.(5)Stepwise regression show that,four factors(CD4+T cell counts,possible infected pathways,PLT,TCM typing)were associated with retention.3 factors(CD4+T cell counts,CD8+T cell counts,possible infected pathways)have a significantly impact on treatment efficiency.Two factors(CD4+T lymphocyte count,BUN)have a significantly impact on CD4+T lymphocyte count recovered to more than 500/μl.Conclusion:KA could stabilize CD4+T cell counts level of HIV/AIDS patients.therapeutic effect and the recovery rate related to baseline CD4+T cell count.KA may improve symptoms and signs,improve quality of life,have a protective effect for blood biochemical indices.KA could delay the HIV/AIDS patients disease progression through Long-term treatment.Part Ⅱ:The study of cellular immune intervention effect of HIV/AIDS patients by treatment with KAObjective:To study the effect of KA on cellular immunity of HIV/AIDS patients.Methods:A prospective cohort study has been applied.Thus,89 HIV/AIDS patients were divied to treated groupP KA group)and untreated group(UK group),for a clinical observation in a period of six months.At 0、3、6 month,Index CD4+T lymphocyte,CD8+T lymphocyte,Treg(CD4+CD25+),NK(CD3-CD16+CD56+),CD8+HLA-DR;chemokine receptor CCR5,CXCR4 in peripheral blood were detected by flow cytometry;The serum cytokines including TNF-α,SCD27,IFN-γ,IL-4,IL-5,apoptosis factor ROS,NF-κB and other indicators were measured by using ELISA kit.Results:(1)At 6 month,compare with the UK group(untreated group),the NK(CD3-CD16+CD56+)of KA group was increased significantly(P<0.05).The TNF-α of KA group was stabilized significantly(P<0.05).the IL-5 and ROS levels of KA group was decreased significantly in peripheral blood of HIV/AIDS patients.(2)Among patients with baseline CD4+T cell<350cells/ul,at 3 month,compare with the UK group,the CD4+T cell counts of KA group significantly increased,the CD8+HL,A-DR of KA group significantly decreased.At 6 month,the CD4+T cell counts of KA group significantly increased,the Treg(CD4+CD25+)of KA group was stabilized significantly(P<0.05),and the CD8+HLA-DR of KA group significantly decreased.(3)Among patients with baseline CD4+T cell≥350 cells/ul,at 6 month,compare with the UK group,the IFN-γ of KA group could significantly increase,and the the sCD27 of KA group was decreased significantly(P<0.05)(4)there was no significant difference of CXCR4 or CCR5 between KA group and UK group(untreated group),There was also no significant difference comparing different grouping by baseline CD4+T cells.Conclusion:KA could have therapeutics effect on stable the immune function of HIV/AIDS patients,and its mechanism may be contributed to enhancing NK,inhibiting cell apoptosis activation,regulating cytokine release.Part Ⅲ:the intervention Research of HIV-1 RNA gene expression for HIV/AIDS patients by treatment with KAObjective:To study the effect of KA on HIV Viral regulatory genes expression of HIV/AIDS patients.Methods:89 HIV/AIDS patients were divied to treated group(KA group)and untreated group(UK group),for a clinical observation in a period of six months.At 0、3、6 month,the HIV-VL were detected by RT-PCR.The relative expression of vpu,tat,vif,nef,rev of patients with HIV-1 were measured by GeXP Multi-gene expression system.Results:(1)Compare with the UK group,the HIV-VL of KA group was no significant difference during 6 month.(2)Baseline indicators Spearman ’analysis showed:nef was negatively related to CD4+T and CCR5,positively related to SCD27.Vpr was negatively related to CD4＋T and NK(CD3-CD16+CD56+),positively related to CD8+HLA-DR.Tat was negatively correlated with CD4+T,CD8+T,Treg(CD4+CD25+),Positively correlated with CD8+HLA-DR.(3)At 3 months,compared with the UK group,the vif of KA group have a significant increased(P<0.05),tat,nef was significantly reduced.At 6 months,compared with the UK group,rev of KA group were significantly decreased(P<0.05).Conclusion:The mechanism of KA effect on HIV/AIDS patients was relevant to the expression inhibition of nef、tat、rev in the level of HIV viral genes expression.Summary:This paper has analysised the characteristics of the effect KA in a long-term clinical application through the retrospective study,explored the action of KA on cellular immune and HIV-1 genes expression of HIV/AIDS patients.The results found that KA could stable immune function of HIV/AIDS patients with symptoms and quality of life improved.It is suggested that KA could have a protective effect for blood,Liver and kidney function.KA can delay the HIV/AIDS patients disease progression through Long-term treatment.Then we found that the mechanism of immune stability of KA may be related to reduce cell activation and apoptosis,immune regulation factor release,and suppress the virus gene expression.The research could provide interpretation and reference to application of traditional Chinese medicine treatment in HIV/AIDS.