CMV viraemia 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 HIV, 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 viraemia and mortality were evaluated using multivariable models, adjusting for baseline HIV viral load, CD4+ percentage, and IL-6 concentrations. Results Baseline CMV viraemia 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% confidence interval (CI) 1.57-4.77). In Uganda (assay limit of detection 120 copies/mL), 89/336 (26%) children had detectable CMV viraemia, 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 CMV viraemia 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 viraemia reduces mortality in children with HIV.