High Epstein-Barr virus (EBV) DNA loads in HIV-infected patients: correlation with antiretroviral therapy and quantitative EBV serology

OBJECTIVE: To study Epstein-Barr virus (EBV) DNA loads in peripheral blood of HIV carriers to determine base-line values and diagnostic relevance of viral load in relation to quantitative serology; to compare EBV presence in parallel plasma and unfractionated whole blood samples; and to correlate EBV DNA load to HIV, CD4 T-cell counts and HAART. DESIGN: One-hundred and nine random patients receiving highly active antiretroviral therapy (HAART) during 1999 and 99 patients on anti-HIV monotherapy during 1993-1996 were included. METHODS: EBV DNA load was determined by quantitative competitive PCR. EBV serology was determined by immunoblot profile and quantitative enzyme-linked immunosorbent assay for responses against VCA-p18 and EBNA-1. RESULTS: Twenty-two out of 109 patients receiving HAART and 28 out of 99 of patients on anti-HIV monotherapy showed elevated EBV DNA loads in whole blood (> 2000 copies/ml), without elevated loads in parallel plasma. EBV DNA load distribution did not differ between the two groups (P = 0.78) and did not correlate with HIV or CD4 T-cell count. In three patients with high EBV DNA loads EBV RNA was virtually absent. Patients with high EBV DNA loads (3610-89 400 copies/ml) had higher anti-VCA-p18 IgG levels than patients with undetectable EBV DNA (P < 0.0001) but lower anti-EBNA-1 IgG levels (P = 0.005). CONCLUSION: Absolute values of EBV DNA load may have poor diagnostic value for defining HIV patients at risk for developing EBV-associated disease. Elevated EBV DNA loads are cell-associated and are not influenced by HAART. Increased anti-p18-VCA and decreased anti-EBNA-1 IgG levels in patients with high EBV loads indicate impaired latency control and increased lytic replication suggesting disturbed overall immunosurveillance against EBV