Lymphoma diagnosis and plasma Epstein-Barr virus load during vicriviroc therapy: results of the AIDS Clinical Trials Group A5211.

TitleLymphoma diagnosis and plasma Epstein-Barr virus load during vicriviroc therapy: results of the AIDS Clinical Trials Group A5211.
Publication TypeJournal Article
Year of Publication2009
AuthorsTsibris AMN, Paredes R, Chadburn A, Su Z, Henrich TJ, Krambrink A, Hughes MD, Aberg JA, Currier JS, Tashima K, Godfrey C, Greaves W, Flexner C, Skolnik PR, Wilkin TJ, Gulick RM, Kuritzkes DR
JournalClin Infect Dis
Volume48
Issue5
Pagination642-9
Date Published2009 Mar 1
ISSN1537-6591
KeywordsAcquired Immunodeficiency Syndrome, Adult, Anti-HIV Agents, DNA, Viral, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Humans, Lymphoma, Male, Middle Aged, Piperazines, Pyrimidines, Viral Load
Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: CCR5 antagonism by vicriviroc treatment in treatment-experienced patients was not associated with reactivation of EBV infection.

DOI10.1086/597007
Alternate JournalClin. Infect. Dis.
PubMed ID19191652
PubMed Central IDPMC2756462
Grant ListAI055038 / AI / NIAID NIH HHS / United States
AI060354 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069419 / AI / NIAID NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
M01 RR000096-478528 / RR / NCRR NIH HHS / United States
RR016482 / RR / NCRR NIH HHS / United States
RR024996 / RR / NCRR NIH HHS / United States
RR02635 / RR / NCRR NIH HHS / United States
T32 AI007387 / AI / NIAID NIH HHS / United States
U01 AI069532 / AI / NIAID NIH HHS / United States
U01 AI069532-03 / AI / NIAID NIH HHS / United States