The Contribution of Kaposi's Sarcoma-Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus-Infected Patients Being Investigated for Tuberculosis in South Africa.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
31 07 2019
Historique:
received: 29 01 2019
accepted: 11 04 2019
pubmed: 21 4 2019
medline: 22 5 2020
entrez: 21 4 2019
Statut: ppublish

Résumé

Despite increasing numbers of human immunodeficiency virus (HIV)-infected South Africans receiving antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of mortality. Approximately 25% of patients treated for TB have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi's sarcoma-associated herpesvirus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for TB. Six hundred eighty-two HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for TB, and followed for 12 weeks. KSHV serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated. Median CD4 count was 62 (range, 0-526) cells/μL; KSHV seropositivity was 30.7% (95% confidence interval [CI], 27%-34%); 5.8% had detectable KSHV-VL (median, 199.1 [range, 13.4-2.2 × 106] copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted odds ratio, 6.5 [95% CI, 1.3-32.4]) in patients without TB or other microbiologically confirmed coinfections (n = 159). Six patients had "possible KSHV-inflammatory cytokine syndrome" (KICS): 5 died, representing significantly worse survival (P < .0001), and 1 patient was diagnosed with KSHV-associated multicentric Castleman disease at autopsy. Given the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed TB, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.

Sections du résumé

BACKGROUND
Despite increasing numbers of human immunodeficiency virus (HIV)-infected South Africans receiving antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of mortality. Approximately 25% of patients treated for TB have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi's sarcoma-associated herpesvirus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for TB.
METHODS
Six hundred eighty-two HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for TB, and followed for 12 weeks. KSHV serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated.
RESULTS
Median CD4 count was 62 (range, 0-526) cells/μL; KSHV seropositivity was 30.7% (95% confidence interval [CI], 27%-34%); 5.8% had detectable KSHV-VL (median, 199.1 [range, 13.4-2.2 × 106] copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted odds ratio, 6.5 [95% CI, 1.3-32.4]) in patients without TB or other microbiologically confirmed coinfections (n = 159). Six patients had "possible KSHV-inflammatory cytokine syndrome" (KICS): 5 died, representing significantly worse survival (P < .0001), and 1 patient was diagnosed with KSHV-associated multicentric Castleman disease at autopsy.
CONCLUSIONS
Given the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed TB, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.

Identifiants

pubmed: 31004430
pii: 5475547
doi: 10.1093/infdis/jiz180
pmc: PMC6667800
doi:

Substances chimiques

Anti-Retroviral Agents 0
Cytokines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

841-851

Subventions

Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : Wellcome Trust
ID : 105165/Z/14/A
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098316
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203135/Z/16/Z
Pays : United Kingdom

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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Auteurs

Melissa J Blumenthal (MJ)

Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.

Charlotte Schutz (C)

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
Department of Medicine, University of Cape Town, South Africa.
Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa.

David Barr (D)

Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa.
Wellcome Trust Liverpool Glasgow Centre for Global Health Research, Institute of Infection and Global Health, University of Liverpool, United Kingdom.

Michael Locketz (M)

Division of Anatomical Pathology, National Health Laboratory Service, University of Cape Town, South Africa.

Vickie Marshall (V)

Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, National Institutes of Health, Maryland.

Denise Whitby (D)

Viral Oncology Section, AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, National Institutes of Health, Maryland.

Arieh A Katz (AA)

Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.

Thomas Uldrick (T)

Fred Hutchison Cancer Research Center, Seattle, Washington.

Graeme Meintjes (G)

Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
Department of Medicine, University of Cape Town, South Africa.
Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa.

Georgia Schäfer (G)

Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.

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Classifications MeSH