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Quantification of HIV-DNA and residual viremia in patients starting ART by droplet digital PCR: Their dynamic decay and correlations with immunological parameters and virological success.
Journal of Clinical Virology ( IF 4.0 ) Pub Date : 2019-06-14 , DOI: 10.1016/j.jcv.2019.06.004
Claudia Alteri 1 , Rossana Scutari 2 , Christof Stingone 3 , Gaetano Maffongelli 3 , Marta Brugneti 2 , Francesca Falasca 4 , Salvatore Martini 5 , Ada Bertoli 2 , Ombretta Turriziani 4 , Loredana Sarmati 3 , Nicola Coppola 5 , Massimo Andreoni 3 , Maria Mercedes Santoro 2 , Carlo-Federico Perno 1 , Francesca Ceccherini-Silberstein 2 , Valentina Svicher 2
Affiliation  

BACKGROUND Accurate quantification of total HIV-DNA and residual-viremia by sensitive assays is extremely useful to optimize monitoring of ART-treated patients. OBJECTIVES To evaluate the performances of two ddPCR-based assays for HIV-DNA and residual-viremia quantification, and the correlations of pre-ART HIV-DNA with plasma HIV-RNA, CD4 + T, CD4/CD8 and virological-success (VS) during first-line ART. STUDY DESIGN Plasma HIV-RNA, total HIV-DNA, CD4 + T, CD4/CD8 were evaluated at baseline of ART, at VS (viral-load <50copies/ml), and at 6 months after VS (6moVS) in 57 newly-diagnosed HIV-1 infected patients, receiving first-line modern ART. HIV-DNA (log10 copies/106CD4 + T) and residual-viremia (copies/ml) were measured with in-house ddPCR assays. Correlations were assessed by Spearman and Jonckheere-Terpstra tests. RESULTS HIV-DNA and residual-viremia assays showed a good linear trend between the expected and obtained values (R2 = 0.9913 and 0.9945); lower limits of detection were 32 copies/106CD4 + T and 2 copies/ml, respectively. At baseline, median (IQR) plasma HIV-RNA and HIV-DNA were 4.88(4.28-5.36)log10 copies/ml and 4.00(3.36-4.51) log10 copies/106CD4 + T cells. Residual-viremia was 8(2-26) and 4(2-12) copies/ml at VS and 6moVS. Pre-ART HIV-DNA positively correlated with plasma HIV-RNA at BL (Rho = 0.708, p < 0.001), and with residual-viremia at VS (Rho:0.383,p = 0.002). Notably, higher HIV-DNA correlated with longer time to achieve VS (median[IQR],weeks: 17.8[12.3-29.0] for HIV-DNA ≥4.5 vs. 7.4[4.1-8.7] for HIV-DNA<4.5, p < 0.001). Furthermore, pre-ART HIV-DNA negatively correlated with CD4 + T and CD4/CD8 at baseline, VS and 6moVS. CONCLUSIONS Our results support the adoption of ddPCR-based assays for both HIV-DNA and residual-viremia quantifications and corroborate that pre-ART HIV-DNA is an excellent indicator in predicting viroimmunological response and VS in patients starting ART.

中文翻译:

通过液滴数字PCR对开始ART的患者中的HIV-DNA和残留病毒血症进行定量:它们的动态衰减以及与免疫学参数和病毒学成功的相关性。

背景技术通过灵敏测定法对总HIV-DNA和残留病毒血症的准确定量对优化ART治疗患者的监测非常有用。目的评估两种基于ddPCR的HIV-DNA和残留病毒血症定量检测的性能,以及ART-HIV HIV-DNA与血浆HIV-RNA,CD4 + T,CD4 / CD8和病毒学成功率(VS)的相关性)在一线ART中进行。研究设计在57例新发现的ART基线,VS(病毒载量<50copies / ml)以及VS后6个月(6moVS)的血浆HIV-RNA,总HIV-DNA,CD4 + T,CD4 / CD8进行了评估。确诊的HIV-1感染患者,接受一线现代抗逆转录病毒治疗。HIV-DNA(log10拷贝/ 106CD4 + T)和残留病毒血症(拷贝/ ml)通过内部ddPCR测定法进行测量。相关性通过Spearman和Jonckheere-Terpstra检验进行评估。结果HIV-DNA和残留病毒血症检测结果显示预期值和获得值之间具有良好的线性趋势(R2 = 0.9913和0.9945);最低检测限分别为32拷贝/ 106CD4 + T和2拷贝/ ml。在基线时,血浆(IQR)血浆HIV-RNA和HIV-DNA分别为4.88(4.28-5.36)log10个拷贝/ ml和4.00(3.36-4.51)log10个拷贝/ 106CD4 + T细胞。在VS和6moVS时,残留病毒血症为8(2-26)和4(2-12)拷贝/ ml。ART前的HIV-DNA与BL的血浆HIV-RNA正相关(Rho = 0.708,p <0.001),而与VS的残留病毒血症呈正相关(Rho:0.383,p = 0.002)。值得注意的是,较高的HIV-DNA与获得VS的时间更长相关(中位数[IQR],周:HIV-DNA≥4.5的周数为17.8 [12.3-29.0],而HIV-DNA <4.5的周数为7.4 [4.1-8.7],p < 0.001)。此外,前ART HIV-DNA在基线,VS和6moVS与CD4 + T和CD4 / CD8呈负相关。
更新日期:2019-06-14
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