Study On Immune Function Reconstruction Of AIDS Patients Treated With Long - Term Antiretroviral Therapy

[Objective]:Our study aims to analyse the characteristics of the immune reconstitution of HIV/AIDS patients after long-term highly active antiretroviral therapy (HAART).[Methods]:We enrolled31adult patients from HIV/AIDS research center of Peking Union Medical Collage Hospital in an identical follow-up manner at the out-patient department from Oct2002to Sep2013. They were followed from baseline to eight years. T cell subset and plasma viral load were done at baseline and month3,6,12,18,24,30,36,42,48,54,60,66,72,78,84,90, and96. Lymphcyte subsets included B cell count (CD19+), NK cell count (CD16+CD56+), CD4+and CD8+T cell count(CD3+CD4+, CD3+CD8+), naive CD4+T cell count(CD4+CD45RA+CD62L+), memory CD4+T cell count(CD4+CD45RA-RO+), CD8+T cell activated subset (CD8+CD38+/CD8+, CD8+HLA-DR+/CD8+), CD4and CD8+T cell functional subsets counts (CD4+CD28+/CD4+、CD8+CD28+/CD8+, and CD4:CD8ratio. We grouped31patients into two arms based on the strata CD4+T cell count:group A including22patients (the strata CD4+T cell count less than200/μl) and group B including9patients (the strata CD4+T cell count betweent200/μl and350/μl). We aimed to evaluate the differences in T cell subsets between the two groups.[Results]:1. Compared with the controls, there were significant decrease in NK cell, CD4+T cell, nai’ve CD4+T cell, memory CD4+T cell counts, and CD4/CD8ratio; there were significant increase in memory CD4+T cell percentage, CD8+T cell and CD8+HLA-DR+T cell. The percentage of CD8+CD38+cells from day0to year2was significantly higher than the controls, similar to the controls from year2to year4, and significantly lower than the controls from year4to year8.2. CD4+T cell counts were more than500/μl in41.9%(13/31) patients after8-year HAART.3. There was a biphasic reconstitution a rapid increase during the first6months followed by a more gradual increase throughout8years. After4-year cART, the increases of naive CD4+cell counts and the decreases of the percentage of CD8+CD38+cells were significantly lower.4. In multivariate regression analysis, male sex, elder age, short duration of cART, baseline CD4+cells<200cells/μL, clinical AIDS events, and lower HIV viral load were associated with a less robust CD4+cell response (p<0.05) during the8-year cART. 5. Compared with the patients in group B, the patients in group A had higher percentage of CD8+T cell and memory CD4+T cell, lower CD4+T cell counts and naive CD4+T cell counts (p<0.05)6. In order to determine factors associated with complete immune reconstitution with CD4+T cell count>500cells/μL after8-year treatment, baseline naive CD4+T cell percentage and female were strongly associated with complete immune reconstitution. Based on ROC curve analysis, the cutoff value for the diagnosis of complete immune reconstitution at8-year cART was12.4%for baseline naive CD4+T cells, with a sensitivity of84.6%, a specificity of88.2%[Conclusions]:1. Incomplete immune reconstitution partially existed in HIV-infected patients after long-term HAART.2. ART should begin at early stage, since CD4+T cell and naive CD4+T cell were lower when the strata CD4+T cell counts were lower than200/mm3。3. Baseline naive CD4+cell percentage may serve as a good prognostic index for complete immune reconstitution during long-term therapy.