Influence Of TwHF Treatment On The Immune Reconstitution And Immune Activation Of Chronic AIDS Patients

Background and Objectives:With the combined antiretroviral therapy(cART),most HIV infected adults could achieve sustained viral suppression.However,15-30%of the HIV infected adults could not reach a satisfactory restore in the CD4+ T cell count,even after long term HIV suppression.This condition is coined,incomplete immune reconstitution.Patients with this condition is called immune non-responders(INRs)or inadequate responders(InaRs).One of the most crucial mechanisms causing incomplete immune reconstitution is immune activation,which is also found to be related to HIV associated non-AIDS conditions and the sustainment of HIV reservoir.This study aims to investigate whether TwHF,an immune suppressing agent widely used in the treatments of autoimmune diseases,could downgrade the level of immune activation in patients with incomplete immune reconstitution and affect the HIV reservoir,and to confirm whether TwHF could have a lasting improving effect over the immune reconstitution state of the patients with immune reconstitution failure by comparing the TwHF treated patients with matching non-TwHF treated control patients.Methods:Eighteen HIV infected adults meeting the criteria for incomplete immune reconstitution were selected from the patients at Peking Union Medical College Hospital.A thearputic dosage of TwHF extract was added to their background cART for 12 months,during which,regular follow-ups were made every three months and after ceasing the addition of TwHF follow-ups were made every six months,at which,clinical information was collected and peripheral blood were taken for the measurement of T lymphocyte subsets,and full blood and plasma were stored for HIV-DNA and inflammatory markers measurements respectively.A control group of non-TwHF treated patients with incomplete immune reconstitution were retrospectively selected and matched,then the CD4+ T cell increase slope of these patients was analysed and compared with TwHF treated patients.Results:1.The influence of TwHF on the T cell subsets in the patients with incomplete immune reconstitutionFor patients in the TwHF group,a combined treatment of TwHF and cART for 12 months achieved a significant increase in the CD4+ T cell count(from 188±61/?l to 272±79/?l,p<0.0001).The increase in CD4+ T cell count was mainly due to the recovery memory CD4+ T cell.The TwHF treatment started at 2.5 years of cART treatment in average.The CD4+ T cell increase slope during TwHF treatment is higher than before TwHF treatment(34.0 cells/mm3/y to 82.0 cells/mm3/y,p=0.077);the increase slope after TwHF treatment ceasing is significantly lower than during the TwHF treatment(82.0 cells/mm3/y to 23.5 cells/mm3/y,p=0.029);slope of non-TwHF treated control group during 0.5-3.5 years of cART ws 27 cells/mm3/y,which is significantly lower than the slope of TwHF group during the TwHF treatment(p=0.022).2.The influence of TwHF on the plasma inflammation markers of the patients with incomplete immune reconstitution13 plasma inflammation markers were measured using the stored plasma obtained at 1 year previous than the start point of TwHF treatment,start point of TwHF treatment,0.5 year and 1 year during TwHF treatment.After the iniatiation of TwHF treatment,IP-10,MIP-1?,MCP-1,IFN-a2,IL-15 and IL-12p40 levels were significantly lowered at at least upon one of the two time points during TwHF treatment,0.5 year or 1 year(p<0.05).Correlation analyses reveal that out of the two types of IFN,IP-10 level is significantly positively correlated to IFN? level.3.The effect of TwHF on HIV reservoir in the patients with incomplete immune reconstitutionNo significant change was found within the HIV-DNA slopes before,during and after TwHF treatment.Conclusion:1.In patients with incomplete immune reconstitution,TwHF increased the CD4+ T cell count and the CD4+ T cell increase slope significantly.The increase of CD4+ T cell count mainly benefited the recovery of memory CD4+ T cell.The increase in the slope of CD4+ T cell change could not be maintained after ceasing the TwHF treatment.2.TwHF treatment lowered IP-10,MIP-1?,MCP-1,IFN-?2,IL-15 and IL-12p40 levels in patients with incomplete immune reconstitution,especially in IP-10,which was found to be significantly correlated to IFN y.3.TwHF treatment did not show significant influences over the HIV reservoir of patients with incomplete immune reconstitution.