Journal Article

Incidence and Outcome of Progressive Multifocal Leukoencephalopathy over 20 Years of the Swiss HIV Cohort Study

Nina Khanna, Luigia Elzi, Nicolas J. Mueller, Christian Garzoni, Matthias Cavassini, Christoph A. Fux, Pietro Vernazza, Enos Bernasconi, Manuel Battegay and Hans H. Hirsch

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 10, pages 1459-1466
Published in print May 2009 | ISSN: 1058-4838
Published online May 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/598335
Incidence and Outcome of Progressive Multifocal Leukoencephalopathy over 20 Years of the Swiss HIV Cohort Study

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Background. We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)–infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996.

Methods. From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996–2007).

Results. The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20–0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04–0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome–defining conditions (P=.007) but similar CD4+ T cell counts (60 vs. 71 cells/µL; P=.25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44–140 days), compared with 90 days (interquartile range, 54–313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8–115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.–60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07–0.50; P<.001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/µL, 0.52; 95% CI, 0.32–0.85; P=.010) and cART use (hazard ratio, 0.37; 95% CI, 0.19–0.75; P=.006).

Conclusions. cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependant on cART use and baseline CD4+ T cell count.

Journal Article.  4553 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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