| 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 dynamics and impact factors of HIV-1 DN A in patients who initiated combined antiretroviral therapy(cART)during chronic infection,to establish a statistical model to predict the possibility of achieving low level of HIV-1 DNA(<100 copies/106 PBMCs)after long terms of effective cART.Methods:A total of 607 chronically HIV-1-infected and treated patients were included in this study.Among them,490 patients were screened from two established national multicenter cohorts.Another 117 outpatients were regularly followed in the clinic of infectious diseases in Peking Union Medical College Hospital.All patients have completed at least two years of cART,achieved viral inhibition(viral load<50 copies/mL)within half a year,and maintained viral inhibition during follow-up.All patients had complete baseline and 96-week data.Real-time quantitative PCR method was used to quantify total HIV-1 DNA in periphery blood samples.Generalized estimating equations and binary logistic regression were used to establish HIV-1 DNA prediction model.Results:1.There was no difference in the level of HIV-1 DNA in whole blood and PBMCs from 22 patients(mean±SD,2.89±0.42 versus 2.87±0.38 log10 copies/106 PBMCs,p = 0.573);Pearson correlation coefficient was 0.925(p<0.001);The intraclass correlation coefficient was 0.920(p<0.001);and the 95%limits of agreement(95%LoA)by Bland-Altman method was-0.293?0.332.2.During long term and effective cART,the level of HIV-1 DNA presented two phases of change.In the first phase,from baseline(3.04±0.47 log10 copies/106 PBMCs)to week 24(2.51±0.48 log10 copies/106 PBMCs),the HIV-1 DNA rapidly decreased.In the second phase,the HIV-1 DNA remained unchanged since week 24.After two years(96 weeks)of cART,92(18.8%)had a low HIV-1 DNA level(<100 copies/106 PBMCs).Factors associated with low level of HIV-1 DNA at week 96 included low baseline HIV-1 DNA and high baseline CD4 count.A mathematic model based on these two factors could well predict the possibility of achieving low level of HIV-1 DNA after long term and effective treatment(sensitivity = 71.67%,specificity = 80.17%).In patients with higher level of HIV-1 DNA before and(or)after treatment,the CD4 count was lower and the proportions of patients with CD4<200 cells/?L was larger.3.21(4.3%,21/490)patients with a low baseline HIV-1 DNA(median,2.0 log10 copies/106 PBMCs)achieved ultralow levels of cell-associated HIV-1 DNA(<20 copies/106 PBMCs)after two years of cART.They also presented with a lower CD8+T-cell count(mean ± SD,511 ± 191 versus 715 ± 256 cells/?L,p=0.013)and a higher CD4/CD8 ratio(1.04 ± 0.37 versus 0.72 ± 0.32,p = 0.002)at week 96.Patients with a higher CD4/CD8 ratio at week 96 were more likely to have levels of HIV-1 DNAbelow the detection limit(per 0.1 increase,OR= 1.29,95%CI,1.05-1.59,p = 0.017).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.The dynamics of total HIV-1 DNA presented two phases of decay after antiretroviral treatment.Baseline HIV-1 DNA and CD4 were independent factors that predicted the low HIV-1 DNA outcome(<100 copies/106 PBMCs).After matching baseline HIV-1 DNA levels,a higher CD4/CD8 ratio at week 96 was the only factor associated with an ultralow level of HIV-1 DNA(<20 copies/106 PBMCs).3.The level of HIV-1 DNA is closely related to disease progression and immune reconstruction.Higher level of HIV-1 DNA correlated with lower CD4 count and larger proportions of partients with AIDS.4.A mathematic model based on baseline DNA and CD4 can well predict the possibility of achieving low level of HIV-1 DNA(<100 copies/106 PBMCs)after 96 weeks of cART(sensitivity = 71.67%,specificity = 80.17%). |
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