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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.

Author information

1
University of California San Diego, San Diego, CA, USA.
2
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
3
Rush University Medical Center, Chicago, IL, USA.
4
Case Western Reserve University, Cleveland, OH, USA.
5
University of California San Francisco, San Francisco, CA, USA.

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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