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

• Published in: The Journal of infectious diseases 2019-07, Vol.220 (5), p.841-851
• Main Authors: Blumenthal, Melissa J, Schutz, Charlotte, Barr, David, Locketz, Michael, Marshall, Vickie, Whitby, Denise, Katz, Arieh A, Uldrick, Thomas, Meintjes, Graeme, Schäfer, Georgia
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; Antiretroviral therapy; Autopsy; Castleman's disease; CD4 antigen; CD4 Lymphocyte Count; Cohort Studies; Coinfection - mortality; Coinfection - virology; Cytokines; Epidemiology; Female; Herpesvirus 8, Human; HIV; HIV Infections - complications; HIV Infections - drug therapy; Hospitals; Human immunodeficiency virus; Humans; Inflammation; Kaposi's sarcoma; Kaposis sarcoma; Major and Brief Reports; Male; Middle Aged; Mortality; Odds Ratio; Patients; Peripheral blood; Sarcoma; Sarcoma, Kaposi - mortality; Sarcoma, Kaposi - pathology; Sarcoma, Kaposi - virology; South Africa - epidemiology; Tuberculosis; Tuberculosis - complications; Viral Load; Young Adult
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz180

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.