Background: Progressive multifocal leukoencephalopathy (PML) is a neurological disease most often seen among immunosuppressed patients. The incidence of PML increased with an increasing incidence of HIV/AIDS. We describe recent trends and the epidemiology of PML-associated death in the era of highly active antiretroviral therapy (HAART). Methods: National multiple-cause-of-death data for the USA were used to identify records with PML listed as a cause of death during 1979–2005. Age-adjusted PML-associated death rates were calculated overall and by sex, race, region and HIV status. Results: The PML-associated death rates peaked in the mid-1990s and decreased from 2.76 deaths per 1 million persons in 1992–1995 to 0.66 in 2002–2005. This decrease was mainly due to a decreasing death rate among PML decedents with HIV diagnosis, males and those aged 20–49 years at death. A decline in death rate was also seen among PML decedents without HIV diagnosis, although this trend was not significant. Decedents in the latter time period were more often female, and older. The proportion of HIV-associated deaths from PML decreased between 1992–1995 (1.4%) and 2002–2005 (1.0%). Conclusion: PML mortality has decreased significantly since 1996 when HAART became the standard of care in the USA. This decline likely reflects increased survival among HIV-positive persons who receive HAART.

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