Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

Frederik Neess Engsig; Ann-Brit Eg Hansen; Lars Haukali Omland; Gitte Kronborg; Jan Gerstoft; Alex Lund Laursen; Court Pedersen; Christian Backer Mogensen; Lars Nielsen; Niels Obel; Frederik Neess Engsig; Ann-Brit Eg Hansen; Lars Haukali Omland; Gitte Kronborg; Jan Gerstoft; Alex Lund Laursen; Court Pedersen; Christian Backer Mogensen; Lars Nielsen; Niels Obel

doi:10.1086/595299

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

Frederik Neess Engsig, Ann-Brit Eg Hansen, Lars Haukali Omland, Gitte Kronborg, Jan Gerstoft, Alex Lund Laursen, Court Pedersen, Christian Backer Mogensen, Lars Nielsen, Niels Obel, Frederik Neess Engsig, Ann-Brit Eg Hansen, Lars Haukali Omland, Gitte Kronborg, Jan Gerstoft, Alex Lund Laursen, Court Pedersen, Christian Backer Mogensen, Lars Nielsen, Niels Obel

161 Citations (Scopus)

Abstract

BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. Conclusions: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.

Original language	English
Journal	Journal of Infectious Diseases
Volume	199
Issue number	1
Pages (from-to)	77-83
Number of pages	6
ISSN	0022-1899
DOIs	https://doi.org/10.1086/595299 https://doi.org/10.1086/595299
Publication status	Published - 2009

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Engsig, F. N., Hansen, A-B. E., Omland, L. H., Kronborg, G., Gerstoft, J., Laursen, A. L., Pedersen, C., Mogensen, C. B., Nielsen, L., Obel, N., Engsig, F. N., Hansen, A-B. E., Omland, L. H., Kronborg, G., Gerstoft, J., Laursen, A. L., Pedersen, C., Mogensen, C. B., Nielsen, L., & Obel, N. (2009). Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. Journal of Infectious Diseases, 199(1), 77-83. https://doi.org/10.1086/595299, https://doi.org/10.1086/595299

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. / Engsig, Frederik Neess; Hansen, Ann-Brit Eg; Omland, Lars Haukali et al.

In: Journal of Infectious Diseases, Vol. 199, No. 1, 2009, p. 77-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Engsig, FN, Hansen, A-BE, Omland, LH, Kronborg, G , Gerstoft, J, Laursen, AL, Pedersen, C, Mogensen, CB, Nielsen, L, Obel, N, Engsig, FN, Hansen, A-BE, Omland, LH, Kronborg, G , Gerstoft, J, Laursen, AL, Pedersen, C, Mogensen, CB, Nielsen, L & Obel, N 2009, 'Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study', Journal of Infectious Diseases, vol. 199, no. 1, pp. 77-83. https://doi.org/10.1086/595299, https://doi.org/10.1086/595299

Engsig FN, Hansen A-BE, Omland LH, Kronborg G , Gerstoft J, Laursen AL et al. Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study. Journal of Infectious Diseases. 2009;199(1):77-83. doi: 10.1086/595299, http://dx.doi.org/10.1086/595299

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title = "Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study",

abstract = "BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. Conclusions: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.",

author = "Engsig, {Frederik Neess} and Hansen, {Ann-Brit Eg} and Omland, {Lars Haukali} and Gitte Kronborg and Jan Gerstoft and Laursen, {Alex Lund} and Court Pedersen and Mogensen, {Christian Backer} and Lars Nielsen and Niels Obel and Engsig, {Frederik Neess} and Hansen, {Ann-Brit Eg} and Omland, {Lars Haukali} and Gitte Kronborg and Jan Gerstoft and Laursen, {Alex Lund} and Court Pedersen and Mogensen, {Christian Backer} and Lars Nielsen and Niels Obel",

note = "Keywords: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cognition Disorders; Cohort Studies; Demography; Denmark; Female; HIV Infections; Humans; Incidence; Leukoencephalopathy, Progressive Multifocal; Male; Risk Factors; Seizures; Speech Disorders; Survival Analysis; Treatment Outcome; Vision Disorders",

year = "2009",

doi = "10.1086/595299",

language = "English",

volume = "199",

pages = "77--83",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "1",

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TY - JOUR

T1 - Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

AU - Engsig, Frederik Neess

AU - Hansen, Ann-Brit Eg

AU - Omland, Lars Haukali

AU - Kronborg, Gitte

AU - Gerstoft, Jan

AU - Laursen, Alex Lund

AU - Pedersen, Court

AU - Mogensen, Christian Backer

AU - Nielsen, Lars

AU - Obel, Niels

AU - Engsig, Frederik Neess

AU - Hansen, Ann-Brit Eg

AU - Omland, Lars Haukali

AU - Kronborg, Gitte

AU - Gerstoft, Jan

AU - Laursen, Alex Lund

AU - Pedersen, Court

AU - Mogensen, Christian Backer

AU - Nielsen, Lars

AU - Obel, Niels

N1 - Keywords: Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Cognition Disorders; Cohort Studies; Demography; Denmark; Female; HIV Infections; Humans; Incidence; Leukoencephalopathy, Progressive Multifocal; Male; Risk Factors; Seizures; Speech Disorders; Survival Analysis; Treatment Outcome; Vision Disorders

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. Conclusions: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.

AB - BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. Conclusions: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.

U2 - 10.1086/595299

DO - 10.1086/595299

M3 - Journal article

C2 - 19007313

SN - 0022-1899

VL - 199

SP - 77

EP - 83

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

Abstract

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