Dataset Information

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.

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.

SUBMITTER: Gianella S

PROVIDER: S-EPMC7239326 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Gianella Sara S Moser Carlee C Vitomirov Andrej A McKhann Ashley A Layman Laura L Scott Brianna B Caballero Gemma G Lada Steven S Bosch Ronald J RJ Hoenigl Martin M Lurain Nell N Landay Alan A Lederman Michael M MM Hunt Peter W PW Smith Davey D

AIDS (London, England) 20200501 6

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Design</h4>We performed a case--control study of PWH starting ART and H ...[more]

PMID: 32271250

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Project description:HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Dataset Information

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.

Background

Objective

Design

Methods

Results

Conclusion

Publications

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.

Similar Datasets

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