Dynamics of Epstein-Barr virus in HIV-1-infected subjects on highly active antiretroviral therapy

Objective: Patients infected with HIV-1 are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. This study evaluated the impact of highly active antiretroviral therapy (HAART) on EBV infection. Methods: To measure EBV content in peripheral blood lymphocytes (PBL) and in plasma, we set up a quantitative analysis using the real-time PCR. EBV latent membrane protein 1 (LMP1) expression was determined by reverse transcriptase-PCR. Results: EBV levels were determined in 33 HIV-1- and EBV-coinfected patients at the start of HAART and during therapy. At baseline, EBV content in PBL samples ranged from 8 to 14 532 copies/mug DNA. EBV levels transiently increased in nine out of 17 patients in whom HIV-1 plasmaviraemia declined to undetectable levels (virological response) and CD4 cell counts increased (immunological response), while they remained fairly stable or decreased in the other eight virological and immunological responders, and in seven patients who showed a virological response only. Of interest, a significant increase in EBV load was observed in five out of nine patients who showed an increase in CD4 cell counts but lack of HIV-1 suppression during HAART. This EBV increase was accompanied by the detection of both LMP1 transcripts in PBL and EBV DNA in plasma, and was paralleled by an increase in immunoglobulin levels, a marker of B-cell stimulation. Conclusions: These findings suggest that peripheral immune reconstitution during HAART without a reduction in HIV-1 replication may increase B-cell stimulation and the number of EBV-infected B cell