Ellis, Jayne; Bangdiwala, Ananta S; Skipper, Caleb P; Tugume, Lillian; Nsangi, Laura; Matovu, John; Pastick, Katelyn A; Ssebambulidde, Kenneth; Morawski, Bozena M; Musubire, Abdu K; +6 more... Schleiss, Mark R; Moore, David AJ; Jarvis, Joseph N; Boulware, David R; Meya, David B; Castelnuovo, Barbara; (2023) Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV. Open Forum Infectious Diseases, 10 (9). ofad449-. DOI: https://doi.org/10.1093/ofid/ofad449
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Abstract
BACKGROUND: Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. METHODS: We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. RESULTS: We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). CONCLUSIONS: CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Research Centre | TB Centre |
PubMed ID | 37732168 |
Elements ID | 208973 |
Official URL | http://dx.doi.org/10.1093/ofid/ofad449 |
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Filename: Ellis_etal_2023_Baseline-Cytomegalovirus-Viremia-at-Cryptococcal.pdf
Licence: Creative Commons: Attribution 4.0
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