Assessment of Ambiguous Base Calls in HIV-1 pol Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies
Assessment of Ambiguous Base Calls in HIV-1 pol Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies
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DOI：
10.1128/jcm.03289-13
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发表时间：
2014-08-01
影响因子：
9.4
通讯作者：
Kuecherer, Claudia
中科院分区：
文献类型：
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作者：
Meixenberger, Karolin;Hauser, Andrea;Kuecherer, Claudia
在不同的研究人群中，HIV-1 Poll群体序列中模糊碱基调用的比例在不同的研究人群中被证明是增加的，并且已经提出了将感染分类为最近或非最近感染的序列模糊阈值。我们研究的目的是使用来自已知感染持续时间的抗逆转录病毒治疗初治血清转换者的样本来评估序列多义性作为HIV-1发病分析的候选生物标记物(德国HIV-1血清转换者研究)。我们使用来自1,334个血清转换器的2,203个HIV-1 Poll群体序列来评估序列模糊度方法(SAM)。然后，我们对495个血清转换者的723个样本的子集进行了血清学发病率床捕获酶免疫分析(Bed-CEIA)和SAM的比较，并对多分析算法进行了评估，其中包括325个血清转换者的453个样本的Bed-CEIA结果、SAM结果、病毒载量和CD4细胞计数。我们观察到，随着感染时间的延长，序列歧义的比例显著增加。以0.5%的序列歧义阈值最好地识别近期感染，准确率为76.7%。最近的平均持续时间被确定为208天(95%可信区间，196至221天)。在子集分析中，Bed-CEIA的准确率显著高于SAM法(84.6vs75.5%，P<；0.001)，结果符合率为64.2%。此外，多分析算法的准确率并不比Bed-CEIA高(83.4%比84.3%，P=0.786)。总而言之，SAM和包括SAM在内的多分析算法不如BED-CEIA，因此序列歧义的比例不是HIV-1发病率检测的更好的生物标志物。
An increase in the proportion of ambiguous base calls in HIV-1 pol population sequences during the course of infection has been demonstrated in different study populations, and sequence ambiguity thresholds to classify infections as recent or nonrecent have been suggested. The aim of our study was to evaluate sequence ambiguities as a candidate biomarker for use in an HIV-1 incidence assay using samples from antiretroviral treatment-naive seroconverters with known durations of infection (German HIV-1 Seroconverter Study). We used 2,203 HIV-1 pol population sequences derived from 1,334 seroconverters to assess the sequence ambiguity method (SAM). We then compared the serological incidence BED capture enzyme immunoassay (BED-CEIA) with the SAM for a subset of 723 samples from 495 seroconverters and evaluated a multianalyte algorithm that includes BED-CEIA results, SAM results, viral loads, and CD4 cell counts for 453 samples from 325 seroconverters. We observed a significant increase in the proportion of sequence ambiguities with the duration of infection. A sequence ambiguity threshold of 0.5% best identified recent infections with 76.7% accuracy. The mean duration of recency was determined to be 208 (95% confidence interval, 196 to 221) days. In the subset analysis, BED-CEIA achieved a significantly higher accuracy than the SAM (84.6 versus 75.5%, P < 0.001) and results were concordant for 64.2% (464/723) of the samples. Also, the multianalyte algorithm did not show better accuracy than the BED-CEIA (83.4 versus 84.3%, P = 0.786). In conclusion, the SAM and the multianalyte algorithm including SAM were inferior to the BED-CEIA, and the proportion of sequence ambiguities is therefore not a preferable biomarker for HIV-1 incidence testing.