Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa.
Background: Despite increasing numbers of human immunodeficiency virus (HIV)-infected South Africans receiving antiretroviral therapy (ART), tuberculosis remains the leading cause of mortality. Approximately 25% of patients treated for tuberculosis have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi's sarcoma-associated Herpes Virus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for tuberculosis.
Methods: 682 HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for tuberculosis, and followed for 12-weeks. KSHV-serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated.
Results: Median CD4 count was 62 cells/μL (range: 0-526); KSHV-seropositivity was 30.7% (95%CI: 27-34%); 5.8% had detectable KSHV-VL (median 199.1; range: 13.4-2.2x106 copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted OR=6.5 [95%CI: 1.3, 32.4]) in patients without tuberculosis or other microbiologically confirmed co-infections (n=159). Six patients had "possible KSHV-inflammatory cytokine syndrome (KICS)": five died, representing significantly worse survival (p<0.0001), and one was diagnosed with KSHV-associated multicentric Castleman disease at autopsy.
Conclusion: Given the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed tuberculosis, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.
High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients Oksenhendler et al. Blood 2000
Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcoma-associated herpes virus Nador et al. Blood 1996
Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease Soulier et al. Blood 1995
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