title: Lymphoma diagnosis and plasma Epstein-Barr virus load during vicriviroc therapy: results of the AIDS Clinical Trials Group A5211.
abstract: Lack of functional CCR5 increases the severity of certain viral infections, including West Nile virus and tickborne encephalitis. In a phase II trial of the investigational CCR5 antagonist vicriviroc (AIDS Clinical Trials Group protocol A5211), 4 lymphomas occurred in study patients who received vicriviroc. Because of the known association between unregulated Epstein-Barr virus (EBV) replication and lymphoma in immunocompromised patients, we evaluated whether vicriviroc exposure was associated with lymphoma EBV antigen positivity and/or had an effect on plasma levels of EBV DNA.
  
  
  
  Clinical findings for all 4 patients enrolled in the A5211 study who developed lymphoma (2 Hodgkin and 2 non-Hodgkin) were reviewed, and tumor specimens were assessed for evidence of ongoing EBV replication. Longitudinal plasma samples from 116 patients in the A5211 study were analyzed, and EBV DNA was quantified by real-time polymerase chain reaction.
  
  
  
  Plasma EBV DNA was not detected in the 2 patients with non-Hodgkin lymphoma; both patients with Hodgkin lymphoma who had samples tested had EBV DNA levels <3200 copies/mL. One patient with Hodgkin lymphoma had a lymph node core biopsy specimen that was strongly positive for EBV; the other 3 lymphomas were histochemically EBV negative. None of the 116 patients with available samples experienced sustained increases in plasma EBV levels.
  
  
  
  CCR5 antagonism by vicriviroc treatment in treatment-experienced patients was not associated with reactivation of EBV infection.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Athe M N
authors.initials: AM
authors.lastname: Tsibris
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Su
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Henrich
authors.forename: Amy
authors.initials: A
authors.lastname: Krambrink
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Judith A
authors.initials: JA
authors.lastname: Aberg
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.forename: Karen
authors.initials: K
authors.lastname: Tashima
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfrey
authors.forename: Wayne
authors.initials: W
authors.lastname: Greaves
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.forename: Paul R
authors.initials: PR
authors.lastname: Skolnik
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilkin
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D010879:Piperazines; D011743:Pyrimidines; C486781:vicriviroc