Limits...
CMV quantitative PCR in the diagnosis of CMV disease in patients with HIV-infection - a retrospective autopsy based study.

Brantsaeter AB, Holberg-Petersen M, Jeansson S, Goplen AK, Bruun JN - BMC Infect. Dis. (2007)

Bottom Line: With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%.With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection.Our results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Infectious Diseases, Ullevaal University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway. abrant@online.no

ABSTRACT

Background: Patients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease. Earlier studies of patients with HIV infection have demonstrated that the diagnosis is often first made post-mortem. In recent years new molecular biological tests have become available for diagnosis of CMV disease. Although clinical evaluation of tests for diagnosis of CMV disease in HIV-infected individuals is suboptimal without autopsy, no results from such studies have been published. The aim of this study was to explore the diagnostic utility of CMV quantitative polymerase chain reaction (PCR) in plasma from HIV and CMV seropositive patients who died during the period 1991-2002 and in whom autopsy was performed.

Methods: Autopsy was performed in all cases, as part of routine evaluation of HIV-infected cases followed at Ullevaal University Hospital. Of 125 patients included, 53 had CMV disease, 37 of whom were first diagnosed at autopsy. CMV disease was diagnosed either by ophthalmoscopic findings typical of CMV retinitis, biopsy or autopsy. One or two plasma samples taken prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease were analysed by CMV quantitative PCR. Sensitivity, specificity, positive and negative predictive values were calculated for different CMV viral load cut-offs and according to detection of viraemia in one versus two samples.

Results: Twenty-seven of 53 patients with CMV disease (51%) and 10 of 72 patients without CMV disease (14%) had detectable viraemia in at least one sample. Sensitivity and negative predictive value (NPV) of the test, maximised with a cut-off at the test's limit of detection of CMV viraemia (400 copies/mL), were 47% and 70%, respectively. With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%. With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection.

Conclusion: Our results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk.

Show MeSH

Related in: MedlinePlus

CMV quantitative PCR results expressed as ROC curve. Receiver operating characteristic (ROC) curve based on quantitative CMV PCR results in the last available plasma sample prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease. *AUC = area under the curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2194717&req=5

Figure 1: CMV quantitative PCR results expressed as ROC curve. Receiver operating characteristic (ROC) curve based on quantitative CMV PCR results in the last available plasma sample prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease. *AUC = area under the curve.

Mentions: The proportion of cases with CMV disease that have a positive tests (sensitivity) plotted against the proportion of cases without CMV disease that have a positive test (1-specificity) for all measured values of CMV DNA viraemia in the last plasma sample are shown as a receiver operating characteristic (ROC) curve in Figure 1. Using the lowest detectable level of viraemia as cut-off, a maximum sensitivity of 47.2% was attained. However, specificity of 1 (100%) (1-specifity = 0) was attained with a cut-off of 10 000 CMV DNA copies/mL as mentioned above. The diagnostic accuracy of the test, expressed by the area under the curve, was 0.69. This area corresponds to the probability that a random person with the disease has a higher CMV viral load than a random person without CMV disease.


CMV quantitative PCR in the diagnosis of CMV disease in patients with HIV-infection - a retrospective autopsy based study.

Brantsaeter AB, Holberg-Petersen M, Jeansson S, Goplen AK, Bruun JN - BMC Infect. Dis. (2007)

CMV quantitative PCR results expressed as ROC curve. Receiver operating characteristic (ROC) curve based on quantitative CMV PCR results in the last available plasma sample prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease. *AUC = area under the curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194717&req=5

Figure 1: CMV quantitative PCR results expressed as ROC curve. Receiver operating characteristic (ROC) curve based on quantitative CMV PCR results in the last available plasma sample prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease. *AUC = area under the curve.
Mentions: The proportion of cases with CMV disease that have a positive tests (sensitivity) plotted against the proportion of cases without CMV disease that have a positive test (1-specificity) for all measured values of CMV DNA viraemia in the last plasma sample are shown as a receiver operating characteristic (ROC) curve in Figure 1. Using the lowest detectable level of viraemia as cut-off, a maximum sensitivity of 47.2% was attained. However, specificity of 1 (100%) (1-specifity = 0) was attained with a cut-off of 10 000 CMV DNA copies/mL as mentioned above. The diagnostic accuracy of the test, expressed by the area under the curve, was 0.69. This area corresponds to the probability that a random person with the disease has a higher CMV viral load than a random person without CMV disease.

Bottom Line: With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%.With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection.Our results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Infectious Diseases, Ullevaal University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway. abrant@online.no

ABSTRACT

Background: Patients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease. Earlier studies of patients with HIV infection have demonstrated that the diagnosis is often first made post-mortem. In recent years new molecular biological tests have become available for diagnosis of CMV disease. Although clinical evaluation of tests for diagnosis of CMV disease in HIV-infected individuals is suboptimal without autopsy, no results from such studies have been published. The aim of this study was to explore the diagnostic utility of CMV quantitative polymerase chain reaction (PCR) in plasma from HIV and CMV seropositive patients who died during the period 1991-2002 and in whom autopsy was performed.

Methods: Autopsy was performed in all cases, as part of routine evaluation of HIV-infected cases followed at Ullevaal University Hospital. Of 125 patients included, 53 had CMV disease, 37 of whom were first diagnosed at autopsy. CMV disease was diagnosed either by ophthalmoscopic findings typical of CMV retinitis, biopsy or autopsy. One or two plasma samples taken prior to the first diagnosis of CMV disease (alive or at autopsy) or death without CMV disease were analysed by CMV quantitative PCR. Sensitivity, specificity, positive and negative predictive values were calculated for different CMV viral load cut-offs and according to detection of viraemia in one versus two samples.

Results: Twenty-seven of 53 patients with CMV disease (51%) and 10 of 72 patients without CMV disease (14%) had detectable viraemia in at least one sample. Sensitivity and negative predictive value (NPV) of the test, maximised with a cut-off at the test's limit of detection of CMV viraemia (400 copies/mL), were 47% and 70%, respectively. With cut-off at 10 000 copies/mL, specificity and positive predictive value (PPV) were 100%. With a requirement for CMV viraemia in two samples, specificity and PPV were 100% in patients with CMV viraemia above the limit of detection.

Conclusion: Our results indicate that quantitative CMV PCR is best used to rule in, rather than to rule out CMV disease in HIV-infected individuals at high risk.

Show MeSH
Related in: MedlinePlus