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AIDS. 2020 Jan 30. doi: 10.1097/QAD.0000000000002484. [Epub ahead of print]

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

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University of California San Diego, San Diego, CA, USA.
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Rush University Medical Center, Chicago, IL, USA.
Case Western Reserve University, Cleveland, OH, USA.
University of California San Francisco, San Francisco, CA, USA.



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.


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.


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.


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.


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.


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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