Effect Of Combination Of Immune ? And HAART On Immune Function And Immune Activation Of HIV/AIDS Patients

AIDS is characterized by decreased number and impaired function of CD4+T lymphocyte and it is caused by HIV whict attacks CD4+T lymphocyte. High immune activation is considered as the immnunological feature of AIDS and the pathogenesis of AIDS, and it plays a very important role in the onset and progession of AIDS. HAART is the the only proven effective therapy in AIDS treatment, and it can inhibite viral replication and restore the impaired immune function, thus delay the progression of AIDS and reduce mortality of patients. Howerve, with the extensive application of HAART, some problems such as HIV genetic variation caused by the emergence of resistant strains and the side effects of HAART have become more prominent.Since 1987, TCM physician began to treat AIDS with traditional Chinese medicine and a lot of valuable experiences had been accumulated in the clinical practice and scientific research. Although TCM had been found not good at anti-virus, it aims at adjusting the body's immune function, improve clinical symptoms and quality of life. So, in the treatment of AIDS, TCM and HAART can complement each other. Combined application of TCM and HAART will obtain better clinical effect in AIDS treatment. The research is devided into 2 parts:Part?Immune activation of HIV/AIDS patients and correlation between immune activation and disease progressionObjectiveTo learn the levels of immune function and immune activation of HIV/AIDS patients in China and find the correlation between the immune activation and CD4+T lymphocyte and disease progression. And discuss the relevance of immune activation with HIV/AIDS pathogenesis.Methods287 cases of HIV/AIDS patients in different disease stages who never accept HAART before and 40 healthy HIV negtive donors have been involved in the research. Their Immune function and abnormal immune activation markers are detected by flow cytometry counts, and the immune activation markers include CD8+CD38+T cells and CD8+HLA-DR+T cell.Compare the difference of abnormal immune activation between patients of various disease stages. And by Pearson correlation test analysis, the correlation between the immune activation levels and abnormal CD4+T lymphocyte count and disease progression will be found.Results?HIV/AIDS patient's immune function was significantly lower than HIV-negative healthy persons (P<0.001), and immune activation levels were significantly higher than that of HIV-negative healthy individuals (P<0.001).?The immune abnormal activation levels were significantly different between patients of different disease stages (P<0.001).?Correlation analysis showed that there was a significant negative correlation between peripheral blood CD4+T cell counts and CD8+CD38+T cells (r=-0.427, P=0.000) and CD8+ HLADR+T cells (r=-0.272, P=0.000).Conclusion1. Compared with healthy HIV-negative pelple, the immune function of HIV/AIDS patients was decreased significantly and the abnormal immune activation levels in HIV/AIDS patients were significantly increased.2. The immune activation levels were different between HIV/AIDS patients of different disease stages, and the immune activation is increased with the disease progression and plasma CD4+T cell counts is related negtively with immune activation markers.3. Immune activation induced by HIV infection may lead to decreased CD4+T cell count and disease progression.Part II Effect of Immune 1 combined HAART on immune function and immune activation of HIV/AIDS patientsObjective To observe the effect of combination of Immune 1 and HAART on the immune function and the abnormal activation and to evaluate the effect of combination of Immune 1 and HAART on the symptoms and signs and the quality of life in the treatment of HIV/AIDS patients.And evaluate the clinical effect and safy of combination of Immune 1 and HAART and to investigate the possible targets and mechanisms of Immune 1. MethodsA randomized, blinded, placebo-controlled clinical trial is designed in which 228 patients who's CD4+T cell count less than 350cells/ul were randomly divided into treatment group and control group, patients from treatment group received Immune 1 combined HAART therapy, patients from control group was given placebo combined HAART. And the observation period is 6 months. Before treatment and 1 month,3 months,6 months after treatment, laboratory data of patients were collected include CD4+T cells counts and their subsets, abnormal immune activation markers (CD8+CD38+T cells and CD8+HLA-DR+T cell), CD8+T cells counts and plasma viral load and also clinical symptoms, signs, Karnofsky score, quality of life and other information were collected. When the trial is finished, the laboratory data and the clinical information will be analized to find which therapy is better in the treatment of HIV/AIDS.Results228 HIV/AIDS patients were enrolled in the clinical trial. During the trial, in the control group,7 patients were not in accordance with inclusion cretirea,1 patient died due to AIDS complication,11 patients failed to follow-up,6 patients stopped taking their medication because of HAART adverse reactions. In the treatment group,6 patients were not in accordance with inclusion cretirea,6 patients failed to follow-up, 4 patients stopped taking their medication because of HAART adverse reactions, and all other 187 patients were involved in the statistical analysis. Results were as follows:?Efficacy of immune function:In both groups, after treatment, CD4+T cell counts were higher than that of before treatment, but there was no statistically significant difference between the two groups (P>0.05). In both groups, immune reconstitution occured in some patients after 6 months treatment and the immune reconstitution rate were higher in treatment group than control group and the rate was respectively 71.4% and 68.5%. However, the statistic difference was not significant between the two groups (P>0.05). In the patients of different CD4+T cells baseline, the treatment group was found to promte immune reconstitution rate in patients with the baseline CD4+T cells of 200 cells/ul?350cells/ul and it is significantly higher than the control group (P<0.05). The immnune reconstitution rates were not significant between patients in the two groups with different ages and different disease courses (P>0.05). Survival analysis statistical techniques showed that the time of immune reconstitution in the two groups was not significantly different (P>0.05). And the treatment group could significantly improve the patient's memory T cells, and the statistical difference is significant (P<0.05). And the therapeutic effects on naive T cell between the two groups were not significantly different.?Efficacy of abnormal immune activation: After treatment, the immune abnormal activation markers was significantly reduced than before treatment, and after 6 months treatment, the difference between the two group was significantly (P<0.05), and it was characterized by CD8+HLA-DR+T cell count significantly reduced.?Efficacy of viral load:After treatment, viral load was significantly lowered in patients of both groups, but difference between groups was not significant (P>0.05).?Efficacy of symptoms and signs:After treatment, some patients's symptoms and signs were reduced and even disappeared in some patients but the differences between the two groups after 1 month treatment and 3 months were not statistically significant (P>0.05) and the differences between the two groups after 6 months treatment were statistically significantly different (P<0.01), and the efficacy of the treatment group was higher than the control group. For single symptom, the treatment group is better in improving patients poor appetite, diarrhea than the control group, the difference was statistically significant (P<0.05); and there is no significant difference between the two groups in improving other symptoms (P>0.05).?Efficacy of Quality of life:In both groups, total scores of MOS-HIV PRO were higher than that of before treatment, but the difference between the 2 groups was not significant (P>0.05).In the fields of energy/fatigue and health feeling, the scores of treatment group were significantly higher than that of control group (P<0.05).?Efficacy of KPS scores:After treatment, the scores of KPS were increased in both groups at each time point, but the efficacy between the two groups was not significant different (P>0.05).?safety analysis:during the trial, advers events occurred in both groups but incidence of adverse events between the two groups were not significant different (P>0.05) and other laboratory indexes were not found abnormal in the two groups during the trial. Conclusion1. Immune 1 combined HAART can effectively promote the immune reconstitution of patients with high CD4+T cells baseline level (200cell/ul?350cell/ul) and increase the body's memory T cell counts and improve the abnormal immune activation status of HIV/AIDS patients and rectify the abnormal immune activation may be the target of Immune 1.2. Immune 1 combined HAART can effectively improve the HIV/AIDS patients' symptoms and signs, especially for the gastrointestinal symptoms and signs such as poor appetite and diarrhea.3. Immune 1 combined HAART can improve the quality of life of HIV/AIDS patients measured by MOS-HIV PRO, especially to improve patient's energy status and health perception.4. Immune 1 combined HAART showed little side effect and is safe to treat HIV/AIDS disease.