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Epstein–Barr virus biomarkers have no prognostic value in HIV-related Hodgkin lymphoma in the modern combined antiretroviral therapy era

Lupo, Juliena; Germi, Raphaëlea; Lancar, Rémib; Algarte-Genin, Michèleb; Hendel-Chavez, Houriac; Taoufik, Yassined; Mounier, Nicolase; Partisani, Marialuisaf; Bonnet, Fabriceg; Meyohas, Marie-Carolineh; Marchou, Brunoi; Semanova, Touyanaa; Prevot, Sophiej; Costagliola, Dominiqueb; Morand, Patricea,*; Besson, Carolinek,*

doi: 10.1097/QAD.0000000000002129

Objectives: Epstein–Barr virus (EBV) has been implicated in lymphomagenesis of HIV-related classical Hodgkin lymphoma (HIV-cHL). The utility of EBV molecular and serological biomarkers has scarcely been examined in HIV-cHL in the recent combined antiretroviral therapy (cART) era.

Design: We evaluated EBV DNA load and a panel of EBV antibodies in HIV-cHL patients prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015.

Methods: Pretreatment whole blood, plasma EBV DNA load and serological profiles were analysed in 63 HIV-infected patients diagnosed with cHL. For the 42 patients with available material, comparisons were performed between values at diagnosis and 6 months after the initiation of chemotherapy.

Results: Pretreatment whole blood and plasma EBV DNA loads were positive in 84 and 59% of HIV-cHL patients, respectively. Two-year progression-free survival estimates did not differ between the patients with pretreatment whole blood (n = 53) or plasma (n = 37) EBV DNA(+) and the patients with pretreatment whole blood (n = 10) or plasma (n = 26) EBV DNA(−) (92 vs. 80% or 89 vs. 92%, P = 0.36 and 0.47, respectively). At diagnosis, 47% of patients harboured an EBV reactivation serological profile. Following chemotherapy, whole blood and plasma EBV DNA levels significantly declined from medians of 1570 [interquartile range, 230–3760) and 73 (0–320) copies/ml to 690 (0–1830) and 0 (0–0) copies/ml, respectively (P = 0.02 and P < 0.0001, respectively]. Anti-EBV IgG antibody level significantly dropped at 6-month follow-up (P = 0.004).

Conclusion: Whole blood and plasma EBV DNA loads do not constitute prognostic markers in HIV-cHL patients in the modern cART era.

aInstitut de Biologie Structurale (IBS), CEA, CNRS, Université Grenoble-Alpes; Laboratoire de Virologie, Centre hospitalier Universitaire Grenoble-Alpes, Grenoble

bINSERM, Sorbonne Université, Institut Pierre Louis d’Epidémiologie et de Santé Publique (IPLESP)

cAP-HP, Hôpitaux Paris Sud, Service d’Immunologie biologique

dINSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases; Université Paris Sud; AP-HP Hôpitaux Paris Sud, Service d’Immunologie biologique, Le Kremlin-Bicêtre, Paris

eDépartement d’Hémato-Oncologie, Archet Hospital, Nice

fHôpitaux Universitaires, Centre de soins de l’infection VIH, Strasbourg

gCHU Bordeaux, Service de Médecine Interne et Maladies Infectieuses; INSERM U593, Université de Bordeaux, Bordeaux

hAP-HP CHU Saint-Antoine, Service de maladies infectieuses, Paris

iCHU Toulouse, Service de maladies infectieuses, Toulouse

jAP-HP, Hôpitaux Paris Sud Site Béclère, Service d’anatomo-pathologie; Université Paris Sud, Le Kremlin-Bicêtre

kINSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre; Unité d’Hémato-Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France; Université Versailles Saint Quentin en Yvelines, Université Paris-Saclay, Paris, France.

Correspondence to Julien Lupo, Dr Laboratoire de Virologie, Centre hospitalier Universitaire de Grenoble, CS 10217, 38043 Grenoble cedex 9, France. Tel: +33476766613; fax: +33476765228; e-mail:; Dr Caroline Besson, MD, PhD, Department of Hematology, Centre Hospitalier de Versailles, 177, rue de Versailles, 78150 LE Chesnay, France. Tel: +33 1 39 63 85 11; fax: +33 1 39 63 94 08; e-mail: cbesson@ch-versailles

Received 21 September, 2018

Revised 6 December, 2018

Accepted 7 December, 2018

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