Owens D K, Holodniy M, Garber A M, Scott J, Sonnad S, Moses L, Kinosian B, Schwartz J S
Section of General Internal Medicine, Veterans Affairs Palo Alto Health Care System, CA 94304 USA.
Ann Intern Med. 1996 May 1;124(9):803-15. doi: 10.7326/0003-4819-124-9-199605010-00004.
To do a meta-analysis of studies that have evaluated the sensitivity and specificity of polymerase chain reaction (PCR) assay for the diagnosis of human immunodeficiency virus (HIV) infection in adults. Evaluating the performance of PCR is difficult because in certain clinical situations, the sensitivity or specificity of PCR may exceed those of the current reference standard tests (enzyme immunoassay followed by confirmatory Western blot analysis). Therefore, an additional goal was to develop recommendations for 1) the design of future evaluative studies of PCR and 2) the use of PCR in persons with suspected HIV infection.
Studies published between 1988 and 1994 that were identified in a search of 17 computer databases, including MEDLINE, and abstracts identified from conference proceedings.
Studies were included if DNA amplification by PCR was done on peripheral blood mononuclear cells from adults. Ninety-six studies met the inclusion criteria.
Data were extracted independently by two reviewers. Study design was assessed independently by two investigators blinded to study results.
Reported sensitivities for PCR range from 10% to 100%, and specificities range from 40% to 100%. A summary receiver-operating characteristic curve based on all 96 studies has a maximum joint sensitivity and specificity (upper left point on the curve, where sensitivity equals specificity) of 97.0% to 98.1%. If the threshold value that defines a positive PCR result is chosen so that sensitivity is higher than 98.1%, specificity will decrease to less than 98.1%. Conversely, if the threshold value that defines a positive PCR result is chosen so that specificity is greater than 98.1%, sensitivity will decrease to less than 98.1%. If sensitivity and specificity are chosen to be equal, the corresponding false-positive rate is 1.9% to 3.0%. At the maximum joint sensitivity and specificity, the positive predictive value of PCR ranges from 34% to 85% as the prevalence of HIV increases from 1.0% to 10%. We identified seven areas in which study design could be modified to 1) reduce susceptibility to bias in estimates of the sensitivity and specificity of PCR and 2) to increase the generalizability of the study results. These modifications will also help to overcome methodologic problems created by the lack of a reference standard test.
The PCR assay is not sufficiently accurate to be used for the diagnosis of HIV infection without confirmation. Use of PCR for the diagnosis of HIV in adults should be limited to situations in which antibody tests are known to be insufficient. Future studies of PCR performance should be sufficiently large and should use adequate reference standard tests and standardized methods for the performance of PCR. Specimens should be evaluated by persons blinded to clinical status and to the results of other diagnostic tests for HIV infection.
对评估聚合酶链反应（PCR）检测法诊断成人人类免疫缺陷病毒（HIV）感染的敏感性和特异性的研究进行荟萃分析。评估PCR的性能存在困难，因为在某些临床情况下，PCR的敏感性或特异性可能超过当前的参考标准检测方法（酶免疫测定法，随后进行确证性免疫印迹分析）。因此，另一个目标是为以下方面制定建议：1）未来PCR评估性研究的设计；2）在疑似HIV感染人群中使用PCR检测。
在对17个计算机数据库（包括MEDLINE）进行检索时确定的1988年至1994年间发表的研究，以及从会议论文集中确定的摘要。
纳入对成人外周血单个核细胞进行PCR DNA扩增的研究。96项研究符合纳入标准。
由两名审阅者独立提取数据。由两名对研究结果不知情的研究者独立评估研究设计。
报告的PCR敏感性范围为10%至100%，特异性范围为40%至100%。基于所有96项研究的汇总受试者工作特征曲线的最大联合敏感性和特异性（曲线左上角的点，此时敏感性等于特异性）为97.0%至98.1%。如果选择定义PCR阳性结果的阈值，使敏感性高于98.1%，则特异性将降至98.1%以下。相反，如果选择定义PCR阳性结果的阈值，使特异性大于98.1%，则敏感性将降至98.1%以下。如果选择敏感性和特异性相等，则相应的假阳性率为1.9%至3.0%。在最大联合敏感性和特异性时，随着HIV流行率从1.0%增加到10%，PCR的阳性预测值范围为34%至85%。我们确定了七个研究设计可修改的方面，以便1）降低PCR敏感性和特异性估计中偏倚的易感性；2）提高研究结果的可推广性。这些修改也将有助于克服因缺乏参考标准检测方法而产生的方法学问题。
在未经确认的情况下，PCR检测法用于诊断HIV感染的准确性不足。成人使用PCR诊断HIV应仅限于已知抗体检测不足的情况。未来对PCR性能的研究应足够大，并应使用适当的参考标准检测方法和标准化的PCR操作方法。标本应由对临床状态和其他HIV感染诊断检测结果不知情的人员进行评估。
