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Presence of asymptomatic CMV and EBV DNA in blood of persons with HIV starting antiretroviral therapy are associated with non-AIDS clinical events.

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

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239326/
No data is associated with this publication.
Abstract

BACKGROUND:Even with antiretroviral therapy (ART), persons with HIV (PWH) experience increased morbidity/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 levels were measured in PBMC. Conditional logistic regression analysis assessed associations and adjusted for relevant covariates; Spearman's correlations compared CMV and EBV levels with other biomarkers. RESULTS:CMV was detected in PBMC of 25% of participants, EBV was detected in > 90%. Higher EBV 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 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 correlated with multiple inflammatory markers and lower CD4/CD8 ratio. CONCLUSIONS:In PWH starting ART, CMV and EBV in PBMC were associated with development of non-AIDS events. Clinical trials will be needed to understand causal mechanisms and ways to interrupt them.

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