Characteristics Of Serum Globulin Changes And Its Relationship With HIV-1 Reservoir And Immune Restoration During Long-term ART

Background:Evaluating the efficacy of antiretroviral therapy（ART）has important guide for guiding clinical medication.In the setting of persistently undetectable plasma viral load,HIV-1 reservoir and immune restoration are the two main clinical indicators for monitoring disease progression and evaluating the efficacy of ART.Serum globulin is a readily available and reliable biomarker in the clinic and has been shown to be an important marker associated with inflammation and infection.Therefore,we speculate that serum globulin may be associated with HIV-1 reservoir size and immune restoration,and may be used as a clinical indicator for evaluating the efficacy of ART.In addition,it was found that the gp120 and gp41 levels of HIV-1-infected patients after receiving stem cell transplantation did not change significantly and the p24 antibody level disappeared.The level of p24 antibody is related to clinical status and can assess the size of the HIV-1 reservoir.However,the characteristics of the changes in p24 antibody and total HIV-1 antibody during long-term ART and their relationship with HIV-1 reservoir have not yet been reported.Objective:This study aimed to investigate the characteristics of serum globulin levels and their relationship with HIV-1 reservoir size and immune restoration during long-term ART.Methods:This study was analyzed using a retrospective cohort,screened according to our inclusion and exclusion criteria,and a total of 27 HIV-1 infected patients met the criteria as our study population.（1）Collect their clinical information including gender,age at initiation of ART,route of infection,ART regimen and serum globulin quantitative value;（2）Detect HIV-1 infection by fluorescent quantitative PCR method in patients receiving ART 0,1,3 The levels of total HIV-1 DNA and cell-associated RNA（CA RNA）at 5 years;（3）The co-expression levels of CD38 and HLA-DR on T cells were detected by flow cytometry;（4）)Plasma concentrations of inflammatory cytokines interferon gamma-inducible protein 10（interferon gamma-inducible protein 10,IP-10）and soluble CD163（s CD163）were detected by enzyme-linked immunosorbent assay（ELISA）;（5）The luciferase immunosorbent assay（LISA）and ELISA were used to detect the levels of p24 antibody and total HIV-1antibody at time points of 0,1,3,and 5 years of ART,respectively.Results:（1）Serum globulin levels in HIV-1 infected patients were abnormally elevated and significantly decreased in the first year of ART.During long-term ART,serum globulin levels were positively correlated with both total HIV-1 DNA and CA RNA,but negatively correlated with CD4⁺T lymphocyte count and CD4/CD8 ratio.In addition,serum globulin was positively correlated with the activation levels of CD4⁺and CD8⁺T lymphocytes and the levels of inflammatory factors IP-10 and s CD163;（2）At 0,1,3,and 5 years of ART,the level of p24 antibody was 2.450,respectively（1.910,5.460）,1.460（1.080,2.160）,1.280（1.120,1.800）,1.570（1.090,2.180）（light unit,LU）;total HIV-1 antibody levels were 3.378（3.157,3.710）,3.489（3.237,3.622）,3.446（2.742,3.573）,3.336（2.860,3.566）.There was no correlation between total HIV-1 antibody level and total HIV-1 DNA and CA RNA（r=0.155,0.165,P>0.05,respectively）;while p24 antibody was positively correlated with total HIV-1 DNA and CA RNA levels（r=0.407,0.305,P<0.05,respectively）;（3）The study found that the CA RNA of 8 HIV-1 infected patients showed increased changes at 3 years of ART,while the total HIV-1 DNA level had no significant difference.Variety.Clinical data showed that these 8 HIV-1 infected patients were complicated by other pathogenic infections at 3 years of ART,and the IP-10 levels of 8 HIV-1 infected patients at 3 years of ART were significantly higher than those of ART 1 year and ART 5 year level.Conclusions:Serum globulin is associated with HIV-1 reservoir size and immune restoration during long-term ART,and can be used as a clinical indicator for evaluating the efficacy of ART;serum globulin component p24 antibody is related to the size of HIV-1 reservoir,Total HIV-1 antibody levels did not correlate with HIV-1reservoir size;co-infection with other pathogens resulted in elevated CA RNA levels but had little effect on total HIV-1 DNA levels.