Strategies Study Of Reducing HIV Resistance By Traditional Chinese Medicine

1 BackgroundAntiviral therapy is the effective means to reduce the incidence and mortality of AIDS.AIDS mortality showed a downward trend,Since 1996,highly effective antiretroviral therapy application,so that,AIDS has become a chronic controllable disease.As of 2009,China’s AIDS treatment coverage of HAART has reached 63.4 percent,The overall mortality of HIV infection among the population decreased from 39.2/100 in 2002 to 14.2/100 in 2009.In the "12th Five-Year" period,With the advance of antiviral treatment time(CD4 count of 350/ul),the number of patients increased significantly,HAART adverse reactions,HIV drug-resistance and many other problems began to appear and become more and more prominent,causing great concern to the academic community.At present,China’s HAART treatment are mainly First Line Regimen(AZT+3TC+EFV/NVP),Adverse drug reactions affect the quality of life and compliance of patients,severe cases can lead to treatment failure.About 25%of patients discontinued treatment because of adverse events during the first year.Some patients worry about drugs adverse reaction,do not follow the prescribed medication,HIV resistance gradually appearance with the increase in the course of treatment,leading to the failure of antiviral therapy.In 12 low-income countries,WHO did surveys in more than 5 thousand people on the acquisition of HIV drug-resistanceduring 2007-2010,The incidence of HIV drug-resistance to any drug was increased from 4.8in 2007 to about 6.8percent in 2010.The patients who experienced virologic failure within the course of the last 12 months,72 percent were drug resistance.A cross-sectional study in Henan in 2007 showed that 230 patients were treated with HAART and the drug resistance rate was up to 70.8-72.3 percent six months later.According to the CDC of STD and AIDS control center released in December 2011,the National AIDS comprehensive prevention and control data information annual report shows that China’s AIDS antiviral treatment overall HIV drug-resistancerate is about 12 percent.Treatment failure due to drug resistance increased mortality.second Line regimen aplication will also increase the cost of treatment.The emergence of the spread of drug-resistant strains(primary drug-resistant cases)makes the treatment more difficult.Therefore,it is of great significanceand highly necessary to study the new scheme and strategy of HIV drug-resistance in the treatment of traditional Chinese medicine,which is based on the clinical difficulties of western medicine.This study relies on "Chinese medicine delaying HIV infection incidence,promote immune reconstitution and decrease the HIV drug-resistance of the clinicalresearch"sub project two second tasks,which is subordinate "Chinese State Key Laboratory for Infectious Disease Develop Grant".A total of 6 hospitals of AIDS epidemic areas implemente the test.I participated in the research task of preliminary design and reporting,responsible for the daily management of the task,clinical monitoring,patient follow-up workandwriting technical summary report,et al,Through the analysis of the experimental data of 600 subjects,the final conclusion was drawn.20bjectiveBy using two kinds of traditional Chinese medicine combined with HAART in the treatment of HIV/AIDS patients,observethe incidence of HIV drug-resistanceand analysis its related factors,Objective to evaluate the clinical efficacy of traditional Chinese medicine and explore a new treatment strategies.3Method3.1 Clinical research methodsIn accordance with the inclusion/exclusion criteria of HIV/AIDS antiviral treatment naive patients,TCM syndrome of spleen kidney yang deficiency syndrome and heat stayinside syndrome who signed the informed consent included in this study.Using a randomized,double-blind,placebo-controlled study of evidence-based medicine,The patients were randomly divided into treatment group and control group according to the proportion of 1:1,two group were given HAART+ Aikeqing capsule/Aifukang capsule,HAART+ Aikeqing capsule placebo/Aifukang capsule placebo treatment.(According to the results of syndrome differentiation treatment,Yang deficiency of spleen and kidney with Aikeqing capsule,heat stayinside syndrome using Aifukang capsule.According to the count of CD4 counts discernible drug,when syndrome differentiation is not distinctness,CD4 below 200 using Aikeqing capsule and CD4 above200using Aifukang capsule).Aikeqing capsule oral,three capsules each time,two times a day.Aifukang capsule oral,every time four tablets,two times a day.The test drug were taken one hour later than antiretroviral drugs.Making a unified case observation table,At the time of follow-up visit,we collected general information,past medical history,recorded HAART regimen,adverse reactions,medication compliance,adverse events,The serum samples were collected from the third party central laboratory to detect the immunological indexes,viral load,HIV genotype resistance and blood and urine routine,liver and kidney function,clinical test adopted Three level quality control,All the clinical data were double entried and collected by the electronic data acquisition system of clinical research.The data will be held after clinical trial,after that,the data verification,cleaning,dividing the data set and eventually locked the data were determined,the data will be analysed by statisticiansaccording to the need of statistical demand.Objective to evaluate the clinical efficacy of two kinds of traditional Chinese medicine combined with HAART therapy in reducing the drug resistance of HIV and the related indexes.3.2 Study on Influencing Factors of HIV drug-resistanceThe related factors affecting the drug resistance were collected by searching the literature of HIV drug-resistance,Design the "HIV drug-resistance influencing factors questionnaire",and attach it to the "case observation form" and fill in the follow-up to analyze the influencing factors of drug resistance.4Results4.1 Clinical research section4.1.1 General information600 patients were enrolled in the study group.According to the data review,581 subjects were admitted to the FAS Set.The results of the group were as follows:there were 288 patients in the treatment group,male 186 cases and female 102 cases,the average age of the patients was 39.83 ± 12.47 years old,while,there were 293 patients in the control group,male 183 cases and female 110 cases,the average age of the patients was 39.96±12.31 years old.76.99 percent the route of infection is sexually transmitted,of which heterosexual transmission accounted for 56.92 percent,men and men homosexual transmission of 20.07 percent,intravenous drug users accounted for 3.63 percent,blood transmission accounted for 5.19 percent,other unexplained infections accounted for 14,19 percent;Patients in the treatment group were 506.41 days from the time of HIV infection to participate in the experiment,the control group was 454.72 days.136 cases were determined with Yang deficiency of spleen and kidney syndrome and 122 cases of toxic heat stayinside syndrome in treatment group,the two types of syndrome were equal to 133 cases in control group.4.1.2 HAART adverse reactionAi Fukang and Ai Keqing capsule can reduce the incidence of adverse reactions of Antiretroviral drugs,the treatment group was 15.98 percent,which was lower than the control group by 2.31 percent,significantly reduce the total score of adverse reactions,the treatment group was 0.23±0.66,while the control group was 0.28±0.75,P value 0.042.Significantly reduce the incidence of fatigue and liver toxicity,meanwhile,significantly reduced the severity of mental disorders and renal toxicity,There was statistical difference between the two groups.At the same time,it can shorten the duration of some adverse reactions.4.1.3viral load and ImmunologyThere was no statistical difference in the absolute value of viral load at each time point,but the inhibition rate was 68.42 percent in the treatment group at week 48,significantly higher than that in the control group(P value 0.049),The results show that the combination of traditional Chinese and Western medicine can improve the success rate of antiviral therapy.After treatment,the CD4 count of two groups showed an upward trend,but there was no difference between the two groups,CD4 count increased 100 cases,the treatment group was significantly better than the control group for 24 weeks,There was no significant difference in other time point.4.1.4 Medication complianceAfter 72 weeks of treatment,the average medication compliance of the treatment group was 95.4 percent,while 89.67 percent in control group and P value 0.039,The results showed that the treatment group had good medication compliance.And HAART medication compliance with HIV load,CD4 showed a good regularity of distribution,that is,the higher the medication compliance,the CD4 level also increased,the failure rate of virological inhibition decreased.4.1.5 DrugresistanceTraditional Chinese medicine combined with HAART treatment group decreased the rate of drug resistance 4.23percent(no statistical difference),In this study,33 kinds of resistance sites were detected,In the treatment group,there were 23 times of drug resistance sites,and the control group was the 48 times,The results showed that the overall level of drug resistance in treatment group was lower than that of HAART alone.The rates of nucleoside resistance site M184V,K65R,and non nucleoside resistance site V1081 in the treatment group were significantly lower than those in the control group.M184V and K65R are the main mutation in lamivudine and tenofovir resistant,Non nucleoside resistance loci V1081 can reduce two times sensibility of nevirapine and efavirenz,It is suggested that traditional Chinese medicine has the potential to prevent drug resistance caused by the mutation site.In the time of drug resistance,the resistance of the treatment group occurred at a later time,In the treatment group,58.33 percent of drug resistance occurred at the point of 48 weeks,and 41.67 percent drug resistance occurred in the 72 weeks,while,70 percent drug resistance occurred at the time of the 48 week,and 30 percent occurred at 72 weeks in control group(P value 0.037),These differences reflect the therapeuticCharacteristic of Chinesemedicine.There was no significant difference between the two groups in the degree of tolerance to a particular class or a drug.Analysis of drug resistance with CD4 cell layering,the drug resistance rate of treatment group was significantly lower than the control group when CD4 above 350 counts,the difference was nostatistically significant when CD4 below 200 counts and between 200 and 350 counts.Chinese medicine should be taken as early as possible to prevent drug resistance.4.1.6 Safety analysisThe incidence of adverse events in the treatment group was lower3.02 percent than that in the control group,but there was no significant difference between the two groups.For 8 weeks and 48 weeks,the treatment group of urine occult incidence was significantly lower than the control group.48weeks,the abnormal rate of the Albumin andGlobulin Ratioin treatment group was significantly lower than control group,The results showed that the traditional Chinese medicine has a good protective effect on liver and kidney function.Other safety indicators did not show statistical differences.4.2 Analysis of influencing factors of drug resistance4.2.1 Analysis of influencing factors of medication complianceSingle factor analysis and multiple factor regression analysis show that,Treatment group,mental workers,AIDSstage,adverse reactions are the factors affecting the medication compliance,medication compliance of Chinese medicine treatment group and AIDS patients is better,medication compliance of the mental workers and the occurrence of adverse reactions to HAART is worse.4.2.2 Analysis of influencing factors of drug resistanceAnalysis of influencing factors of drug resistancendicate that,Different regions(rural and urban),with or without HAART adverse reactions,CD4 count stratification,medication compliance is the influencing factors of drug resistance.The combination of HAART with DT4,interstitial medication and adverse drug reactions were risk factors of drug resistance,And according to the provisions of HAART time and dose of medication,Aikeqing capsual is a protective factor to prevent the occurrence of drug resistance.The results showed that the main influencing factors of drug resistance were related to treatment factors,drug factors and regional factors.5Conclusion(I)Combination of traditional Chinese and Western medicine treatment program to reduce HIV resistance is generally safe and effective,HIV drug-resistance rate was reducedby 4.23 percent,and HAART adverse drug reactions,medication compliance and other related indicators have good clinical efficacy.(2)The main factors affecting drug resistance are drug factors and treatment factors.To solve the problem of drug resistance of HIV should be pitching-in from the clinical point of view.(3)At present,there is no evidence to prove that traditional Chinese medicine can directly reduce or alleviate drug resistance.This study shows that,Based on the idea of prevention,treatingfactors related to drug resistance based on syndrome differentiation of traditional Chinese Medicine,such as antiviral drug adverse reaction and drug compliance,to reduce the drug resistance is feasible.