Conflicting Findings of EBV-Biomarker Use in HIV-Related Lymphomas

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Plasma EBV DNA load has shown a positive correlation with the plasma HIV RNA load, EBV DNA load could be a surrogate marker of a nonoptimal management of HIV infection.
Plasma EBV DNA load has shown a positive correlation with the plasma HIV RNA load, EBV DNA load could be a surrogate marker of a nonoptimal management of HIV infection.

Conflicting findings regarding the association between plasma Epstein-Barr virus (EBV) load in persons living with HIV and HIV-related lymphomas highlights a need for assessment of who benefits from an optimal management of HIV infection and comorbidities, according to a letter to the editor published in Clinical Infectious Diseases.

A recent paper by Muncunill, et al 2 regarding an association between plasma EBV load and HIV-related lymphomas reported that high EBV load (>5000 copies/mL) at lymphoma diagnosis was a negative prognostic factor for overall survival and progression-free survival in patients with HIV-Hodgkin's lymphoma comorbidity and HIV-non-Hodgkin's lymphoma comorbidity. This study concluded that plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-related lymphomas.

However, this study, as well as others, did not find similar associations. This study aimed to assess EBV load in the French ANRS Co16 Lymphovir cohort, which included patients with HIV-Hodgkin's lymphoma (N=83) and non-Hodgkin's lymphoma (N=123) who were enrolled between 2008 and 2015. Results showed that 2-year progression-free survival estimates did not differ between patients with Hodgkin's lymphoma with pretreatment plasma EBV DNA and those with pretreatment plasma EBV DNA: 89% vs 92%, respectively (P =.47).

These discrepancies may be for several reasons. First, Muncunill, et al enrolled patients during a much longer period (1995-2016) than other studies, but the distribution of the patients according to years of enrollment is unknown. The populations of cases were also heterogeneous. Further, the studies varied in what management of HIV infection the patients underwent before the diagnosis of lymphoma. In the Muncunill et al study, only 30% of patients with lymphoma had an undetectable HIV RNA load, raising the issue of the optimal management of HIV infection before lymphoma diagnosis, shown by the high proportion of patients with a CD4 count below 200/µL, which is higher than the 32% to 42% reported in other studies, and by the low frequency of patients (60%) receiving combined antiretroviral therapy.

As a result of plasma EBV DNA load having demonstrated a positive correlation with the plasma HIV RNA load, EBV DNA load could be a surrogate marker of a nonoptimal management of HIV infection and of immunosuppression, which both strongly affect the incidence and the outcome of HIV-related lymphomas. In addition, the 2-year overall survival among patients with HIV-Hodgkin's lymphoma comorbidity reported by Muncunill et al was 74%, which is lower than the multiple, more recently reported 2-year overall survival rates in this demographic of patients (91%-94%). Because survival of patients with HIV has improved within the last years, the prognostic value of plasma EBV DNA load should be reevaluated in a cohort of patients with HIV-lymphoma comorbid illness diagnosed in a more recent period.

Overall, the study authors concluded that, "[g]iven the conflicting findings in these studies, we point out the need for assessment of EBV load in persons living with HIV from the most recent [combined antiretroviral therapy] era who benefit from an optimal management of HIV infection and comorbidities."

Reference

  1. Lupo J, Germi R, Costagliola D, Morand P, Besson B. Utility of Epstein-Barr virus biomarkers in HIV-related lymphomas in the modern combined antiretroviral therapy era [published online September 11, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy786/5094805
  2. Muncunill J, Baptista MJ, Hernandez-Rodríguez Á, et al. Plasma EBV-load as an early biomarker and prognostic factor of HIV-related lymphomas [published online June 29, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy542
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