Journal of Clinical Virology 42 (2008) 433–436 Short communication The predictive value of cerebrospinal fluid Epstein-Barr viral load as a marker of primary central nervous system lymphoma in HIV-infected persons Craig Corcoran a,* , Kevin Rebe b , Helen van der Plas c , Landon Myer d , Diana R. Hardie a a National Health Laboratory Service and Division of Virology, Faculty of Health Sciences, University of Cape Town, South Africa b HIV Unit, GF Jooste Hospital, Mannenberg and Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa c Infectious Diseases Unit, Tygerberg Hospital and Department of Medicine, Stellenbosch University, South Africa d School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, South Africa Received 10 March 2008; received in revised form 20 March 2008; accepted 20 March 2008 Abstract Background: The presence of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) is used as a marker of HIV-associated primary central nervous system lymphoma (PCNSL). In our setting, EBV DNA is frequently detected in the CSF of HIV-infected patients with miscellaneous neurological diseases and thus its presence is a poor predictor of PCNSL. Objectives: To determine whether quantification of EBV DNA in CSF improves its diagnostic specificity for PCNSL. Study design: EBV viral loads were determined on CSF samples from 55 HIV-infected patients with CNS disease. Results: Twenty of the 55 patients had detectable EBV DNA in their CSF (median viral load 6120 copies/ml, range 336–1,034,000 copies/ml). PCNSL was confirmed in 2 patients. Their CSF EBV loads were 1,034,000 and 15,460copies/ml, respectively. Using a cut-off of 10,000copies/ml improved the specificity and positive predictive value (PPV) compared to a qualitative result for the diagnosis of PCNSL (96% vs. 66% and 50% vs. 10%, respectively). Conclusion: EBV DNA is commonly detected in CSF of HIV-infected patients. Quantitative PCR improves the diagnostic specificity, however, the PPV remains too low for it to be used as an isolated marker for PCNSL. © 2008 Elsevier B.V. All rights reserved. Keywords: Primary central nervous system lymphoma; Epstein-Barr virus; EBV PCR; EBV viral load 1. Introduction HIV-infected persons frequently develop disease of the central nervous system (CNS) such as primary CNS lym- phoma (PCNSL), reported to occur in 2–13% of AIDS Abbreviations: AIDS, acquired immune deficiency syndrome; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr virus; FBL, focal brain lesions; HAART, highly active antiretroviral therapy; HIV, human immunodeficiency virus; MRI, magnetic resonance imaging; PPV, positive predictive value; PCNSL, primary CNS lymphoma. * Corresponding author at: Diagnostic Virology, C18, Groote Schuur Hos- pital, Anzio Road, Observatory, 7925 Cape Town, South Africa. Tel.: +27 21 404 5200; fax: +27 21 447 5683. E-mail address: Craig.Corcoran@uct.ac.za (C. Corcoran). patients (Cinque et al., 1997). The majority of AIDS- associated PCNSL are high grade B-cell lymphomas. Epstein-Barr virus (EBV) plays a role in the development of PCNSL and the tumour cells contain a high copy number of EBV genomes (Cinque et al., 1997). Establishing the diag- nosis of PCNSL is difficult as the clinical presentation and radiological features are similar to other CNS mass lesions. The gold standard for establishing a diagnosis is a brain biopsy, however where available, in HIV-infected patients it is associated with considerable morbidity (∼8%) and mortality (∼3%) (Antinori et al., 2000; Skolasky et al., 1999). EBV DNA is frequently detected in the cerebrospinal fluid (CSF) of patients with PCNSL, and early studies found its presence to be a sensitive and specific marker of this malig- nancy (Cinque et al., 1996). As a result, EBV PCR testing has 1386-6532/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jcv.2008.03.017