Abstract
BackgroundPatients 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.MethodsAutopsy 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.ResultsTwenty-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.ConclusionOur 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.
Highlights
Patients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease
Results from our study are likely to be relevant for patients who interrupt treatment, who fail to respond to antiretroviral therapy, or who are diagnosed too late for effective HIV therapy to be initiated. This was a retrospective study in which the time intervals varied considerably between the last plasma sample and CMV diagnosis, or between the last plasma sample and death in cases without CMV disease, as samples were taken as part of routine monitoring of the patients rather than on clinical suspicion
It is likely that the sensitivity and positive predictive value (PPV) of CMV polymerase chain reaction (PCR) will be higher in a setting where plasma is analysed at a time of clinical suspicion of CMV end-organ disease, rather than as part of routine monitoring of patients
Summary
Patients with advanced HIV infection at the time of diagnosis and patients not responding to antiretroviral therapy are at risk of cytomegalovirus (CMV) disease. Not using modern molecular biological methods for CMV disease, demonstrated that CMV disease was under-diagnosed in HIV-infected patients, and that the diagnosis was often first made at autopsy [4,5,6,7,8,9,10]. Newer diagnostic tests may improve the detection rate of CMV disease in this patient population. French guidelines recommend both ophthalmocsopy and testing for CMV viraemia by PCR every three months in patients with CD 4 cell counts below 50–100/mm, whereas U.S guidelines focus on the early clinical recognition of CMV disease [11,12]
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