Investigation of pre-diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients.

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.