title: Investigation of pre-diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients.
abstract: Progressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre-diagnostic biological markers and risk factors for PML are not well understood. We conducted a case-control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV-positive controls, and 50 HIV-negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV-positive controls, and 28% in HIV-negative controls (P = 0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV-positive controls (33%) (P = 0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8-1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P = 0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV-positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2-394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. mgrabows@jhsph.edu
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grabowski
authors.forename: Raphael P
authors.initials: RP
authors.lastname: Viscidi
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Keerti V
authors.initials: KV
authors.lastname: Shah
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D015415:Biomarkers; D001769:Blood / Q000821:virology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014556:Urine / Q000821:virology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D004279:DNA, Viral