title: Lymphoma and Epstein-Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial.
abstract: OBJECTIVE
  Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein-Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients. We assessed whether IL-2 had an impact on EBV replication and the development of lymphoma.
  
  
  METHODS
  A total of 130 ART-naïve patients were randomized to receive IL-2 therapy (n = 66) or no treatment (n = 64). Clinical data for patients with lymphomas were reviewed and tumours assessed for evidence of EBV infection and CD25 (the IL-2 receptor) expression. EBV DNA levels were measured in whole blood and plasma in both arms using real-time polymerase chain reaction (PCR), up to 48 weeks after baseline (BL).
  
  
  RESULTS
  Four lymphomas occurred, a median of 61 weeks [range 40-94 weeks] after randomization at a median CD4 cell count of 396 cells/μL (IQR 234-536 cells/μL). In the IL-2 arm, two patients developed EBV-positive Hodgkin's lymphoma, and one developed EBV-negative Burkitt-type lymphoma. One patient in the control group developed EBV-positive non-Hodgkin's lymphoma. CD25 was negative in all cases. Among the 41 of 55 (control arm) and 44 of 58 (IL-2 arm) patients with detectable EBV DNA in whole blood at both BL and week 48, the median change in EBV DNA between BL and week 48 was +0.04 log10 copies/ml in both arms (P = 0.7). In plasma, EBV was detected at least once in 22 of 52 controls and 21 of 54 IL-2-treated patients (P = 0.8).
  
  
  CONCLUSIONS
  IL-2 therapy had no significant effect on EBV replication over 48 weeks in these ART-naïve patients. The occurrence of lymphomas did not seem to be associated with IL-2 therapy.
authors.affiliation: Department of Infectious Diseases, Saint-Louis Hospital, Paris, France; University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: de Lastours
authors.forename: J
authors.initials: J
authors.lastname: LeGoff
authors.forename: J
authors.initials: J
authors.lastname: Brière
authors.forename: F
authors.initials: F
authors.lastname: Agbalika
authors.forename: T
authors.initials: T
authors.lastname: Boulet
authors.forename: Y
authors.initials: Y
authors.lastname: Lévy
authors.forename: F
authors.initials: F
authors.lastname: Simon
authors.forename: J-P
authors.initials: JP
authors.lastname: Aboulker
authors.forename: J-M
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000097:blood / Q000821:virology*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000097:blood / Q000821:virology*; D006801:Humans; D015994:Incidence; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D007376:Interleukin-2
keywords: Epstein−Barr virus; HIV; interleukin-2; lymphoma