. 2025 Apr 7;44(8):764-771.

doi: 10.1097/INF.0000000000004811.

Clinical and Immunologic Impact of CMV Coinfection Among Children Living With HIV in Canada

Yves Fougère^{1

2}, Jason Brophy³, Michael T Hawkes⁴, Terry Lee⁵, Lindy Samson³, Soren Gantt^{2

6

7}, Mi-Suk Kang Dufour^{2

8}, Christian Renaud^{6

7}, Hinatea Dieumegard^{6

8}, Madeleine Aby Diallo^{6

8}, Jade Canape^{6

8}, Stanley Read⁹, Ari Bitnun⁹, Hugo Soudeyns^{2

6

7

8

9}, Fatima Kakkar^{2

7}; on behalf of the EPIC Study Group

Collaborators, Affiliations

Collaborators

on behalf of the EPIC Study Group:
Ariane Alimenti¹⁰, Petronela Ancuta¹¹, Ari Bitnun¹², Jason Brophy¹³, Jared Bullard¹⁴, Tae-Wook Chun¹⁵, Hélène C F Côté¹⁶, Joanne Embree¹⁴, Michael T Hawkes¹⁷, Fatima Kakkar¹⁸, Christos Karatzios¹⁹, Rupert Kaul²⁰, John Kim²¹, Valérie Lamarre²², Normand Lapointe²², Pascal Lavoie²³, Terry Lee²⁴, Deborah M Money²⁵, Dorothy Moore¹⁹, Stanley Read¹², Robert Reinhard²⁶, Lindy Samson¹³, Paul Sandstorm²⁷, Laura Sauve²⁸, Sandra Seigel²⁹, Joel Singer³⁰, Hugo Soudeyns³¹, Ben Tan³², Wendy Vaudry³³

Affiliations

¹ From the Unit of Pediatric Infectious Diseases and Vaccinology, Department of Woman Mother and Child, Lausanne University Hospital, Lausanne, Switzerland.
² Centre d'infectiologie mère-enfant (CIME), Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, Quebec, Canada.
³ Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
⁴ BC Children's Hospital and Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
⁵ CIHR Pan-Canadian Network for HIV & STBBI Clinical Trials Research (CTN+), Vancouver, British Columbia, Canada.
⁶ Department of Microbiology, Infectiology & Immunology.
⁷ Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
⁸ University of California, Berkeley, School of Public Health.
⁹ Unité d'immunopathologie virale, Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, Quebec, Canada.
¹⁰ British Columbia (BC) Women's Hospital & Health Centre, Vancouver.
¹¹ Centre de recherche du Centre hospitalier de l'Université de Montréal, Department of Microbiology, Infectiology & Immunology, Université de Montréal.
¹² Hospital for Sick Children, Department of Pediatrics, University of Toronto.
¹³ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa.
¹⁴ Children's Hospital of Winnipeg, University of Manitoba.
¹⁵ National Institute of Allergy and Infectious Diseases, Bethesda.
¹⁶ University of British Columbia, Vancouver.
¹⁷ BC Children's Hospital and Department of Pediatrics, University of British Columbia, Vancouver.
¹⁸ Centre hospitalier universitaire (CHU) Sainte-Justine, Department of Pediatrics, Université de Montréal.
¹⁹ Montreal Children's Hospital, Department of Pediatrics, McGill University.
²⁰ University Health Network, Department of Medicine, University of Toronto.
²¹ National Human Immunodeficiency Virus (HIV) and Retrovirology Laboratory (NHRL), Public Health Agency of Canada (PHAC), Winnipeg.
²² CHU Sainte-Justine, Department of Pediatrics, Université de Montréal.
²³ BC Women's & Children's Hospital, Vancouver.
²⁴ Canadian Institutes of Health Research (CIHR) Canadian HIV Trials Network (CTN), Vancouver.
²⁵ BC Women's Hospital & Health Centre, University of British Columbia, Vancouver.
²⁶ Public/Global Health Consultant, San Francisco.
²⁷ NHRL, PHAC, Winnipeg.
²⁸ BC Women's Hospital & Health Centre, Department of Pediatrics, University of British Columbia, Vancouver.
²⁹ McMaster Children's Hospital, Department of Pediatrics, McMaster University, Hamilton.
³⁰ CIHR CTN, Vancouver.
³¹ Centre de recherche Azrieli du CHU Sainte-Justine, Department of Microbiology, Infectiology & Immunology and Department of Pediatrics, Université de Montréal.
³² Department of Pediatrics, University of Saskatchewan, Saskatoon.
³³ Stollery Children's Hospital, Department of Pediatrics, University of Alberta, Edmonton.

PMID: 40209769
PMCID: PMC12240138
DOI: 10.1097/INF.0000000000004811

Clinical and Immunologic Impact of CMV Coinfection Among Children Living With HIV in Canada

Yves Fougère et al. Pediatr Infect Dis J. 2025.

. 2025 Apr 7;44(8):764-771.

doi: 10.1097/INF.0000000000004811.

Authors

Collaborators

on behalf of the EPIC Study Group:
Ariane Alimenti¹⁰, Petronela Ancuta¹¹, Ari Bitnun¹², Jason Brophy¹³, Jared Bullard¹⁴, Tae-Wook Chun¹⁵, Hélène C F Côté¹⁶, Joanne Embree¹⁴, Michael T Hawkes¹⁷, Fatima Kakkar¹⁸, Christos Karatzios¹⁹, Rupert Kaul²⁰, John Kim²¹, Valérie Lamarre²², Normand Lapointe²², Pascal Lavoie²³, Terry Lee²⁴, Deborah M Money²⁵, Dorothy Moore¹⁹, Stanley Read¹², Robert Reinhard²⁶, Lindy Samson¹³, Paul Sandstorm²⁷, Laura Sauve²⁸, Sandra Seigel²⁹, Joel Singer³⁰, Hugo Soudeyns³¹, Ben Tan³², Wendy Vaudry³³

Affiliations

¹ From the Unit of Pediatric Infectious Diseases and Vaccinology, Department of Woman Mother and Child, Lausanne University Hospital, Lausanne, Switzerland.
² Centre d'infectiologie mère-enfant (CIME), Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, Quebec, Canada.
³ Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
⁴ BC Children's Hospital and Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
⁵ CIHR Pan-Canadian Network for HIV & STBBI Clinical Trials Research (CTN+), Vancouver, British Columbia, Canada.
⁶ Department of Microbiology, Infectiology & Immunology.
⁷ Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
⁸ University of California, Berkeley, School of Public Health.
⁹ Unité d'immunopathologie virale, Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, Quebec, Canada.
¹⁰ British Columbia (BC) Women's Hospital & Health Centre, Vancouver.
¹¹ Centre de recherche du Centre hospitalier de l'Université de Montréal, Department of Microbiology, Infectiology & Immunology, Université de Montréal.
¹² Hospital for Sick Children, Department of Pediatrics, University of Toronto.
¹³ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa.
¹⁴ Children's Hospital of Winnipeg, University of Manitoba.
¹⁵ National Institute of Allergy and Infectious Diseases, Bethesda.
¹⁶ University of British Columbia, Vancouver.
¹⁷ BC Children's Hospital and Department of Pediatrics, University of British Columbia, Vancouver.
¹⁸ Centre hospitalier universitaire (CHU) Sainte-Justine, Department of Pediatrics, Université de Montréal.
¹⁹ Montreal Children's Hospital, Department of Pediatrics, McGill University.
²⁰ University Health Network, Department of Medicine, University of Toronto.
²¹ National Human Immunodeficiency Virus (HIV) and Retrovirology Laboratory (NHRL), Public Health Agency of Canada (PHAC), Winnipeg.
²² CHU Sainte-Justine, Department of Pediatrics, Université de Montréal.
²³ BC Women's & Children's Hospital, Vancouver.
²⁴ Canadian Institutes of Health Research (CIHR) Canadian HIV Trials Network (CTN), Vancouver.
²⁵ BC Women's Hospital & Health Centre, University of British Columbia, Vancouver.
²⁶ Public/Global Health Consultant, San Francisco.
²⁷ NHRL, PHAC, Winnipeg.
²⁸ BC Women's Hospital & Health Centre, Department of Pediatrics, University of British Columbia, Vancouver.
²⁹ McMaster Children's Hospital, Department of Pediatrics, McMaster University, Hamilton.
³⁰ CIHR CTN, Vancouver.
³¹ Centre de recherche Azrieli du CHU Sainte-Justine, Department of Microbiology, Infectiology & Immunology and Department of Pediatrics, Université de Montréal.
³² Department of Pediatrics, University of Saskatchewan, Saskatoon.
³³ Stollery Children's Hospital, Department of Pediatrics, University of Alberta, Edmonton.

PMID: 40209769
PMCID: PMC12240138
DOI: 10.1097/INF.0000000000004811

Abstract

Background: Although cytomegalovirus (CMV) disease has been well described among severely immunocompromised children living with HIV (CLWH), the impact of CMV coinfection, is not well understood. The objective of this study was to characterize the clinical and immunologic effects of CMV coinfection in CLWH in Canada.

Methods: This is a substudy of the Early Pediatric Initiation, Canada Child Cure Cohort study, which enrolled CLWH in Canada between 2014 and 2018. CMV serostatus was determined at the first (baseline) study visit, and HIV-1 viral load (VL), CMV VL, and lymphocyte subsets were quantified every 3-6 months. For a subset of participants, CD4 + and CD8 + T cell subsets were analyzed using flow cytometry. The clinical outcomes were recorded retrospectively at the baseline visit and prospectively during the study period.

Results: Of the 225 participants, 85.3% were CMV seropositive (CMV + ) and 81% had suppressed HIV VL. While there were no significant differences in clinical outcomes between CMV + and CMV - children, CMV + children had lower frequencies of CD4 + T cells, higher frequencies of CD8 + T cells, and lower CD4/CD8 ratio at baseline than CMV - children. Children with CMV + children also demonstrated a higher frequency of CD4 + effector memory cells, lower CD8 + naïve T cells, and higher frequencies of CD8 + terminally differentiated effector memory cells. These differences remained significant even after adjusting for HIV viral control.

Conclusions: CMV coinfection is common among CLWH and is associated with distinct immunological changes despite the effective control of HIV replication with antiretroviral therapy. The long-term implications of these immunologic perturbations require further investigation.

Keywords: HIV; T cell subsets; children; coinfection; cytomegalovirus.

PubMed Disclaimer

Conflict of interest statement

The CMV PCR testing kits and the AltoStar platform were donated by Altona Diagnostics. The authors declare the following conflicts: S.G.: consulting fees and/or research support from Moderna, Merck, GSK, VBI, Curevo and Altona. F.K.: research support from Altona, and Honoraria from ViV. The remaining authors declare no conflicts of interest. The funders had no role in the study design; collection, analyses or interpretation of data; writing of the manuscript or decision to publish the results.

Figures

**FIGURE 1.**
Distribution of CD4⁺ and CD8⁺ T cells according to CMV serostatus. A: Relative baseline and nadir frequencies of CD4⁺ and CD8⁺ T cells according to CMV serostatus. B: Baseline and nadir CD4/CD8 ratios according to CMV serostatus.

See this image and copyright information in PMC

References

1. Gianella S, Letendre S. Cytomegalovirus and HIV: a dangerous Pas de Deux. J Infect Dis. 2016;214(Suppl 2):S67–S74. - PMC - PubMed
1. Slyker JA. Cytomegalovirus and paediatric HIV infection. J Virus Erad. 2016;2:208–214. - PMC - PubMed
1. Freeman ML, Lederman MM, Gianella S. Partners in crime: the role of CMV in immune dysregulation and clinical outcome during HIV infection. Physiol Behav. 2016;13:10–19. - PMC - PubMed
1. NIH, Centers for Disease Control and Prevention, HIV Medicine Association of the IDSA. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. 2023. Available at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult.... Accessed January 20, 2025.
1. Nelson M, Dockrell D, Edwards S, et al. ; BHIVA Guidelines Subcommittee. British HIV Association and British Infection Association guidelines for the treatment of opportunistic infection in HIV-seropositive individuals 2011. HIV Med. 2011;12:1–140. Available at: https://www.bhiva.org/file/SwhaEzgXmAGOt/hiv_v12_is2_Iss2Press_Text.pdf. - PubMed

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Clinical and Immunologic Impact of CMV Coinfection Among Children Living With HIV in Canada

Collaborators

Affiliations

Clinical and Immunologic Impact of CMV Coinfection Among Children Living With HIV in Canada

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials