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

Ninety percent to 95% of the adult human population carries Epstein-Barr virus (EBV) as a chronic latent infection; the vast majority of these patients experience no serious sequelae. Healthy adults experience episodes of transient EBV viremia, with EBV DNA levels in whole blood usually <2000 copies/mL [1]. In HIV-infected patients, EBV has been associated with the development of AIDS-related diffuse large cell Hodgkin and Burkitt lymphomas [2]. The CCR5 antagonist maraviroc is approved for treatment-experienced patients with HIV infection [3, 4], and several other agents are in various stages of clinical development [5, 6]. Functional inactivation of CCR5 because of a homozygous 32 amino acid deletion of this protein (CCR5Δ32/CCR5Δ32) is generally well tolerated. However, studies of CCR5 knockout mice and epidemiological data from human CCR5Δ32 homozygotes suggest that this deletion may increase the susceptibility to and severity of certain infections, including tickborne encephalitis and West Nile virus [7–13]. The AIDS Clinical Trials Group (ACTG) protocol A5211 was a randomized, placebo-controlled phase IIb study that assessed the safety and efficacy of the investigational CCR5 antagonist vicriviroc (VCV) in 118 treatment-experienced patients [14]. Among the 118 enrolled participants, 4 of 90 VCV recipients and none of 28 control subjects developed lymphomas within the first 13 months of VCV treatment. In light of the known link between EBV and lymphomas, we explored whether VCV treatment affected the level of EBV viremia over time.