Abstract

BackgroundIn HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear.MethodsIn a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA.ResultsWe analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log10 ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log10 ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log10 copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98).ConclusionsCMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.

Highlights

  • Cytomegalovirus (CMV) latently infects up to 70% of the general population [1]

  • ¤ Current address: Transplant Infectious Diseases, Alberta Institute for Transplantation Sciences and Li Ka Shing Institute for Virology, University of Alberta, Edmonton, Alberta, Canada " Membership of the Swiss human immunodeficiency virus (HIV) Cohort Study is provided in the Acknowledgments

  • Patient Characteristics As of May 2010, 779 cases of incident CMV disease were documented in the Swiss HIV Cohort Study (SHCS)

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Summary

Introduction

Cytomegalovirus (CMV) latently infects up to 70% of the general population [1]. To achieve control of CMV replication and prevent tissue-invasive CMV disease CMV-specific T-cells are essential. In patients with prolonged immunosuppression, substantial reduction of CMV-specific T-cells is associated with an increased risk for CMV reactivation, progressive replication and disease [2]. The decline of CD4 T-cells below 100 cells/mL serves as a surrogate marker for an advanced state of immunosuppression and an increased risk of CMV disease [3,4]. In HIV-infected patients the impact of CMV-specific CD4 T-cells on CMV replication remains controversial. CMV-specific T-cells were shown to poorly predict CMV retinitis in HIV-AIDS patients [8], suggesting a potential role for other (immunological) co-factors. In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear

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