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

AIDS. 2020 May 1;34(6):849-857. doi: 10.1097/QAD.0000000000002484.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Case-Control Studies
  • Cytomegalovirus / genetics
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / blood*
  • Cytomegalovirus Infections / complications
  • DNA, Viral / genetics*
  • DNA, Viral / metabolism
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / complications
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged

Substances

  • DNA, Viral