Journal Article

Lymphoma Diagnosis and Plasma Epstein-Barr Virus Load during Vicriviroc Therapy: Results of the AIDS Clinical Trials Group A5211

Athe M. N. Tsibris, Roger Paredes, Amy Chadburn, Zhaohui Su, Timothy J. Henrich, Amy Krambrink, Michael D. Hughes, Judith A. Aberg, Judith S. Currier, Karen Tashima, Catherine Godfrey, Wayne Greaves, Charles Flexner, Paul R. Skolnik, Timothy J. Wilkin, Roy M. Gulick and Daniel R Kuritzkes

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 5, pages 642-649
Published in print March 2009 | ISSN: 1058-4838
Published online March 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/597007
Lymphoma Diagnosis and Plasma Epstein-Barr Virus Load during Vicriviroc Therapy: Results of the AIDS Clinical Trials Group A5211

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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.

Journal Article.  5294 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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