Study On The Effect Of Tripterygium Wilfordii Combined With Acute And Chronic HIV-1 Infected Patients On The Peripheral Blood HIV-1 DNA Repository And Incomplete Immune Reconstitute

[Objective]The objective of our study is to identify the consistency of peripheral blood mononuclear cells(PBMCs)and whole blood in the quantification of HIV-1 DNA;to study the effects of combination antiretroviral therapy(cART)combined with Tripterygium wilfordii tablets on the changes of HIV-1 DNA in acute patients;to study the effect of Tripterygium wilfordii tablets on CD4+T cell count in chronic patients with incomplete immune reconstitute.[Methods]In this study,a total of 27 patients in acute stage were divided into three groups,standard therapy,intense therapy and the Tripterygium wilfordii(TwHF)therapy group.The median time of adding TwHF in the acute phase was about the 6th month of cART,and lasted for 12 months.At the 18th month of cART,all patients in the three groups were changed to standard therapy.Twenty-seven patients in chronic stage were all patients with incomplete immune reconstitute,and were treated with TwHF as adjuvant therapy.The median time of adding TwHF was about the 30th month of cART and asted for 12 months.Patients were followed up every 3 months for the first 48 months and every 6 months after the 48 months,except for baseline and the first month of treatment.Another 44 patients in chronic phase were included to evaluate the consistency of the whole blood and PBMCs in detecting HIV-1 DNA.Clinical information of patients was recorded,peripheral blood was collected,plasma and PBMCs were separated and frozen,routine test,HIV plasma load detection,lymphocyte subsets detection,etc.Real-time quantitative PCR was used to evaluate the consistency of two samples in detecting HIV-1 DNA,and the level of total HIV-1 DNA in whole blood of patients was determined.The appropriate method was selected for statistical analysis.[Results]1.There was no difference in the level of HIV-1 DNA in whole blood and PBMCs from 44 patients(3.05±0.40 vs 3.02±0.39 log 10copies/106PBMCs);Pearson correlation coefficient was 0.887;and the 95%limits of agreement(95%LoA)by Bland-Altman method was-0.340?0.390 log10copies/106 PBMCs.2.HIV-1 RNA in acute HIV-1 patients decreased to undetectable levels by the 6th month of cART,and HIV-1 RNA in both intense therapy decreased more rapidly than that in the standard therapy group at the beginning of treatment,and basically dropped to undetectable levels by the 3rd month of cART.CD4+T cell count,CD8+T cell count,CD4/CD8 ratio and CD38+CD8+/CD8+%were close to or into the normal range at 3,6,12 and 18 months after treatment,respectively.CD8+T cell count in the TwHF group increased from 6 to 18 months after cART,and decreased from 18 to 72 months after cART.HLA-DR+CD8+/CD8+%in three groups decreased during treatment,but was still higher than normal at 72nd month of follow-up.The level of HIV-1 DNA in standard therapy and intense therapy groups decreased throughout the follow-up period,and the rate of decrease was the fastest in the 6 months before cART.The changes of HIV-1 DNA in the TwHF group in the first 6 months were the same as those in the intense therapy group,and an increasing trend appeared after the 12th month and maintained until the 72nd month.3.Among the 27 patients treated with TwHF,20(74.1%)patients had good recovery of CD4 T cell count(>50cells/ul)at 1 year which were mainly memory CD4 T cells.TwHF can also increase the CD4/CD8 ratio regardless of whether the CD4 count is elevated.Correlation analysis showed that the efficacy of CD4+T cells after TwHF intervention was negatively correlated with cART time before TwHF intervention,and was not correlated with baseline CD4+T cell counts.COX regression analysis showed that age and combined HCV infection were two independent risk factors.[Conclusions]1.The test results of HIV-1 DNA using whole blood and PBMCs were well consistent with each other.Whole blood can replace PBMCs DNA in quantifying HIV-1 DNA.2.HIV-1 DNA levels were affected by TwHF intervention in acute patients,and TwHF could be an activator of a latent reservoir.3.TwHF intervention in chronic patients can effectively improve the phenomenon of incomplete immune reconstitution,which may be caused by the activation of EIF2 signaling pathway and the inhibition of IFN pathway.