Cytomegalovirus viremia as a risk factor for mortality in HIV-associated cryptococcal and tuberculous meningitis
Caleb P Skipper, Katherine Huppler Hullsiek, Fiona V Cresswell, Kiiza Kandole Tadeo, Michael Okirwoth, Mark Blackstad, Nelmary Hernandez-Alvarado, Claudia Fernández-Alarcón, Stewart Walukaga, Emily Martyn, Jayne Ellis, Kenneth Ssebambulidde, Lillian Tugume, Edwin Nuwagira, Joshua Rhein, David B. Meya, David R. Boulware, Mark R. Schleiss
Abstract
OBJECTIVES: CMV viremia is associated with increased mortality in persons with HIV. We previously demonstrated that CMV viremia was a risk factor for 10-week mortality in antiretroviral therapy (ART)-naïve persons with cryptococcal meningitis. We investigated whether similar observations existed over a broader cohort of patients with HIV-associated meningitis at 18 weeks. METHODS: We prospectively enrolled Ugandans with cryptococcal or TB meningitis into clinical trials in 2015-2019. We quantified CMV DNA concentrations from stored baseline plasma or serum samples from 340 participants. We compared 18-week survival between those with and without CMV viremia. RESULTS: IU/ml increase; 95% CI 1.09-1.35; P <0.001) were positively associated with all-cause mortality through 18 weeks. CONCLUSION: CMV viremia at baseline was associated with a higher risk of death at 18 weeks among persons with HIV-associated cryptococcal or TB meningitis, and the risk increased as the CMV viral load increased. Further investigation is warranted to determine whether CMV is a modifiable risk contributing to deaths in HIV-associated meningitis or is a biomarker of immune dysfunction.