Lymphoma diagnosis and plasma Epstein-Barr virus load during vicriviroc therapy: results of the AIDS Clinical Trials Group A5211.
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.
Tsibris
Athe M N
AM
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Paredes
Roger
R
Chadburn
Amy
A
Su
Zhaohui
Z
Henrich
Timothy J
TJ
Krambrink
Amy
A
Hughes
Michael D
MD
Aberg
Judith A
JA
Currier
Judith S
JS
Tashima
Karen
K
Godfrey
Catherine
C
Greaves
Wayne
W
Flexner
Charles
C
Skolnik
Paul R
PR
Wilkin
Timothy J
TJ
Gulick
Roy M
RM
Kuritzkes
Daniel R
DR
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
D019380:Anti-HIV Agents; D004279:DNA, Viral; D010879:Piperazines; D011743:Pyrimidines; C486781:vicriviroc