Patients infected with HIV are at high risk to develop NHL. The incidence increases with age, and the male-to-female ratio is approximately 2:1. Depending on specific histologies, the EBV association ranges from 30% in systemic HIV-related BL, to 70% to 80% in HIV-related DLBCL, and virtually all cases of HIV-related PCNSL are EBV-positive. In biopsies of EBV-associated HIV-NHL, there is considerable variation in the number of EBV-positive cells, and the pattern of EBV latent gene expression varies among tumor types as in immunocompetent individuals (see Fig.1E and F). As dis cussed in the section on EBV-associated B-cell lymphomas, other specific diagnoses that are more prominent in HIV-infected patients include PEL and plasmablastic lymphoma. In addition, HL is EBV positive in upwards of 80% of HIV-related cases.
Fig1. EXAMPLES OF EPSTEIN-BARR VIRUS–POSITIVE LYMPHOID MALIGNANCIES. Posttransplant lymphoproliferative disorder (PTLD), Hodgkin lymphoma, and large B-cell lymphoma. PTLD in the duodenum of a 15-month-old (A) with history of liver transplant. (B) The PTLD was classified as a polymorphic type and was Epstein-Barr virus (EBV)-positive. Hodgkin lymphoma (C) and EBV-positive Reed-Sternberg cells (D). Large B-cell lymphoma (plasmablastic type) in a human immunodeficiency virus–positive patient (E), diffusely EBV-positive (F). Note, all EBV studies are in situ hybridizations for EBV messenger RNA, EBER.
In HIV-infected patients, the development of EBV-associated HIV-NHL is preceded by a loss of functional EBV-specific T cells, suggesting that strategies to boost the endogenous EBV-specific T-cell response might prevent lymphomas. Additional factors known to pre dispose HIV-infected patients to EBV-associated lymphomas include underlying cytokine dysregulation and proinflammatory state. Restoring CD4+ T-cell counts in patients with HIV with highly active antiretroviral therapy (ART) has decreased the incidence of PCNSL and HIV-related DLBCL. The incidence of HIV-related BL, which tends to occur in patients with higher CD4 counts and with less HIV viremia, has remained stable over time despite improved access to ART.
Oral hairy leukoplakia (OHL) develops frequently, although not exclusively, in patients who are HIV-positive. It is a non-malignant hyperplasia of epithelial cells, and most patients present with white, corrugated lesions on the tongue. Besides IM, OHL is the only EBV associated disease in which active viral replication is apparent, and multiple strains are often present within the same lesion. Inhibiting EBV replication in vivo with antivirals such as valacyclovir results in resolution of OHL. However, after valacyclovir treatment, EBV replication recurs in normal tongue epithelial cells, indicating that productive EBV replication is necessary but not sufficient to induce OHL.
