Progressive Multifocal Leukoencephalopathy Deaths in the USA, 1979–2005

Abstract

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.

Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies

“…In the pre-human immunodeficiency virus era PML was anecdotally reported in some patients with myelolymphoproliferative disorders or other forms of cancer, but its incidence significantly increased with the advent of acquired immunodeficiency syndrome, affecting 0.7/1000 persons/year [3]. After the introduction of antiretroviral treatment the incidence (0.07/1000 persons/year) [3] and the mortality of the disease reduced significantly [4,5]. Recently, several cases of PML related to the use of new immunomodulatory compounds for the treatment of several dysimmune diseases were reported, leading to an urgent need for the identification of risk factors and disease biomarkers.…”

The Changing Landscape of Progressive Multifocal Leukoencephalopathy

“…A nationwide Danish study of HIV-associated PML found that the incidence rates declined from 3.3 per 1,000 person-years in 1995-1996 (pre-HAART era) to 1.8 per 1,000 personyears in 1997-1999 (early HAART era) and 1.3 per 1,000 person-years in 2000-2006 (late HAART era) [31]. Similarly, a national multiple-cause-of-death database for the United States confirmed a decline in mortality from HIVassociated PML between the period 1992-1995 and the period 2002-2005; the decline was attributed to HAART [32]. Despite the observed decline in incidence, PML remains a significant central nervous system complication of HIV/AIDS.…”

Infections and multiple sclerosis

“…By the mid-1990s approximately 4% of patents dying of acquired immunodeficiency syndrome (AIDS) had progressive multifocal leukoencephalopathy. With the routine use of highly active antiretroviral therapy in 1996, incidence and death rates of progressive multifocal leukoencephalpathy have gradually declined, though not reaching pre-epidemic levels (Christensen et al, 2010). The demyelinated foci show a loss of oligodendrocytes.…”