Cytomegalovirus Viremia Is Associated With Mortality Among Children With HIV Starting Antiretroviral Therapy in Sub-Saharan Africa
Abstract
Background: Cytomegalovirus (CMV) co-infection is associated with mortality in adults with human immunodeficiency virus (HIV) infection, but whether CMV is associated with mortality in children with HIV remains uncertain.
Methods: In 498 children (median age 6.3 years, interquartile range 2.3–9.6) enrolled in the ARROW trial (ISRCTN24791884) in Uganda (336/498) and Zimbabwe (162/498) selected using a case-cohort design, CMV was quantified using real-time polymerase chain reaction at initiation of non-nucleotide reverse transcriptase inhibitor-based antiretroviral therapy (ART), 12 weeks post-ART, and 84 weeks post-ART. Associations between baseline CMV viremia and mortality were evaluated using multivariable models, adjusting for baseline HIV RNA, CD4+ percentage, and IL-6 concentrations.
Results: Baseline CMV viremia was associated with mortality, with relationships differing by country and assay. In Zimbabwe (assay limit of detection 20 copies/mL), 119/162 (73%) children had detectable CMV, and each log10 higher CMV viral load was associated with over 2-fold higher mortality (adjusted hazard ratio [aHR] = 2.74; 95% CI 1.57–4.77). In Uganda (assay limit of detection 120 copies/mL), 89/336 (26%) children had detectable CMV viremia, which was associated with 3-fold higher mortality compared to undetectable CMV (aHR = 3.15; 95% CI 1.11–8.93). In a subset of 48 children with immunophenotyping data, we found no evidence that CMV was associated with immune activation.
Conclusions: Cytomegalovirus viremia is independently associated with mortality in children with HIV starting ART in sub-Saharan Africa. Future studies should define the underlying mechanisms and evaluate whether suppressing CMV viremia reduces mortality in children with HIV.
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BibTeX
@article{fisayo2026cytomegalovirus,
title = {{Cytomegalovirus Viremia Is Associated With Mortality Among Children With HIV Starting Antiretroviral Therapy in Sub-Saharan Africa}},
author = {Temitope Fisayo and Ceri Evans and Kuda Mutasa and Dagmar Alber and Moira J Spyer and Sandra Rukobo and Mutsa Bwakura-Dangarembizi and Victor Musiime and Kusum J Nathoo and Ade Kekitiinwa and Cissy Kityo and Diana M Gibb and Nigel Klein and A Sarah Walker and Andrew J Prendergast},
journal = {Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America},
year = {2026},
month = jun,
doi = {10.1093/cid/ciag354},
url = {https://doi.org/10.1093/cid/ciag354},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cytomegalovirus Viremia Is Associated With Mortality Among Children With HIV Starting Antiretroviral Therapy in Sub-Saharan Africa
AU - Temitope Fisayo
AU - Ceri Evans
AU - Kuda Mutasa
AU - Dagmar Alber
AU - Moira J Spyer
AU - Sandra Rukobo
AU - Mutsa Bwakura-Dangarembizi
AU - Victor Musiime
AU - Kusum J Nathoo
AU - Ade Kekitiinwa
AU - Cissy Kityo
AU - Diana M Gibb
AU - Nigel Klein
AU - A Sarah Walker
AU - Andrew J Prendergast
PY - 2026
DA - 2026/06/09
JO - Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
DO - 10.1093/cid/ciag354
UR - https://doi.org/10.1093/cid/ciag354
AB - Background: Cytomegalovirus (CMV) co-infection is associated with mortality in adults with human immunodeficiency virus (HIV) infection, but whether CMV is associated with mortality in children with HIV remains uncertain. Methods: In 498 children (median age 6.3 years, interquartile range 2.3–9.6) enrolled in the ARROW trial (ISRCTN24791884) in Uganda (336/498) and Zimbabwe (162/498) selected using a case-cohort design, CMV was quantified using real-time polymerase chain reaction at initiation of non-nucleotide reverse transcriptase inhibitor-based antiretroviral therapy (ART), 12 weeks post-ART, and 84 weeks post-ART. Associations between baseline CMV viremia and mortality were evaluated using multivariable models, adjusting for baseline HIV RNA, CD4+ percentage, and IL-6 concentrations. Results: Baseline CMV viremia was associated with mortality, with relationships differing by country and assay. In Zimbabwe (assay limit of detection 20 copies/mL), 119/162 (73%) children had detectable CMV, and each log10 higher CMV viral load was associated with over 2-fold higher mortality (adjusted hazard ratio [aHR] = 2.74; 95% CI 1.57–4.77). In Uganda (assay limit of detection 120 copies/mL), 89/336 (26%) children had detectable CMV viremia, which was associated with 3-fold higher mortality compared to undetectable CMV (aHR = 3.15; 95% CI 1.11–8.93). In a subset of 48 children with immunophenotyping data, we found no evidence that CMV was associated with immune activation. Conclusions: Cytomegalovirus viremia is independently associated with mortality in children with HIV starting ART in sub-Saharan Africa. Future studies should define the underlying mechanisms and evaluate whether suppressing CMV viremia reduces mortality in children with HIV.
SN - 1058-4838
SN - 1537-6591
ER -