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

Abstract

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.

• Authors: Melissa J Blumenthal, Charlotte Schutz, David Barr, Michael Locketz, Vickie Marshall, Denise Whitby, Arieh A Katz, Thomas Uldrick, Graeme Meintjes, Georgia Schäfer
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 220 Issue 5 Pg. 841-851 (07 31 2019) ISSN: 1537-6613 [Electronic] United States
• PMID: 31004430 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Anti-Retroviral Agents
• Cytokines

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Retroviral Agents (therapeutic use)
• CD4 Lymphocyte Count
• Cohort Studies
• Coinfection (mortality, virology)
• Cytokines
• Female
• HIV Infections (complications, drug therapy)
• Herpesvirus 8, Human
• Hospitals
• Humans
• Male
• Middle Aged
• Odds Ratio
• Sarcoma, Kaposi (mortality, pathology, virology)
• South Africa (epidemiology)
• Tuberculosis (complications)
• Viral Load
• Young Adult