Presence of asymptomatic cytomegalovirus and Epstein-Barr virus DNA in blood of persons with HIV starting antiretroviral therapy is associated with non-AIDS clinical events

Sara Gianella, Carlee Moser, Andrej Vitomirov, Ashley McKhann, Laura Layman, Brianna Scott, Gemma Caballero, Steven Lada, Ronald J. Bosch, Martin Hoenigl, Nell Lurain, Alan Landay, Michael M. Lederman, Peter W. Hunt, Davey Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Even with antiretroviral therapy (ART), persons with HIV (PWH) experience increased morbidity and mortality. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections likely exacerbate inflammatory-related diseases. Objective: To determine if presence of detectable CMV or EBV DNA in peripheral blood mononuclear cells (PBMC) is associated with non-AIDS events among PWH receiving modern ART. Design: We performed a case-control study of PWH starting ART and HIV-suppressed at year 1 and thereafter, 140 cases who experienced non-AIDS events and 305 matched controls. Events included myocardial infarction, stroke, malignancy, serious bacterial infection or death. Methods: Blood samples were studied pre-ART, 1-year post-ART and pre-event. Controls had an event-free follow-up equal or greater than cases. CMV and EBV DNA levels were measured in PBMC. Conditional logistic regression analysis assessed associations and adjusted for relevant covariates; Spearman's correlations compared CMV and EBV DNA levels with other biomarkers. Results: CMV DNA was detected in PBMC of 25% of participants, EBV DNA was detected in more than 90%. Higher EBV DNA levels were associated with increased risk of events at all time points (odds ratio (OR) per one IQR=1.5-1.7, all P<0.009). At year 1, detectable CMV DNA was associated with increased risk of events in most adjusted models (OR=1.4-1.8, P values ranging 0.03-0.17). Higher levels of CMV and EBV DNA correlated with multiple inflammatory markers and lower CD4+/CD8+ ratio. Conclusion: In PWH starting ART, detection of CMV and EBV DNA in PBMC was associated with development of non-AIDS events. Clinical trials will be needed to understand causal mechanisms and ways to interrupt them.

Original languageEnglish (US)
Pages (from-to)849-857
Number of pages9
JournalAIDS
Volume34
Issue number6
DOIs
StatePublished - May 1 2020
Externally publishedYes

Keywords

  • cytomegalovirus and Epstein-Barr virus DNA
  • HIV
  • inflammation
  • non-AIDS events
  • non-AIDS mortality
  • viral suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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