ritonavir and Epstein-Barr-Virus-Infections

We compared primary Epstein-Barr virus (EBV) infection and suppression between Kenyan human immunodeficiency virus-infected infants starting nevirapine-based vs lopinavir/ritonavir-based antiretroviral regimens. Although the rate of EBV infection was similar between groups, infants receiving lopinavir/ritonavir suppressed EBV more rapidly. Our findings suggest that specific antiretrovirals may potentially impact the risk of future EBV-associated malignancies.

Topics: Anti-HIV Agents; Drug Therapy, Combination; Epstein-Barr Virus Infections; HIV Infections; Humans; Infant; Kenya; Lopinavir; Nevirapine; Risk Factors; Ritonavir

Epstein-Barr Virus (EBV)-associated immunoblastic lymphoma occurs in immunocompromised patients such as those with AIDS or transplant recipients after primary EBV infection or reactivation of a preexisting latent EBV infection. In the present study, we evaluated the effect of ritonavir, an HIV protease inhibitor, on EBV-positive lymphoblastoid B cells in vitro and in mice model. We found that it induced cell-cycle arrest at G1-phase and apoptosis through down-regulation of cell-cycle gene cyclin D2 and antiapoptotic gene survivin. Furthermore, ritonavir suppressed transcriptional activation of NF-kappaB in these cells. Ritonavir efficiently prevented growth and infiltration of lymphoma cells in various organs of NOD/SCID/gammacnull mice at the same dose used for treatment of patients with AIDS. Our results indicate that ritonavir targets NF-kappaB activated in tumor cells and shows anti-tumor effects. These data also suggest that this compound may have promise for treatment or prevention of EBV-associated lymphoproliferative diseases that occur in immunocompromised patients.

Topics: Animals; Apoptosis; Blotting, Western; Cell Cycle; Cell Movement; Cell Proliferation; Electrophoretic Mobility Shift Assay; Epstein-Barr Virus Infections; Herpesvirus 4, Human; HIV Protease Inhibitors; Humans; In Situ Hybridization, Fluorescence; Lymphoma, B-Cell; Mice; NF-kappa B; Polymerase Chain Reaction; Ritonavir; Transcriptional Activation; Xenograft Model Antitumor Assays

We report a case of rapidly progressive solid lymphoma with anaplastic large cell morphology, followed by systemic Kaposi sarcoma in an adult patient with AIDS. The lymphoma cells expressed human herpesvirus 8 (HHV-8)-encoded latent and lytic proteins and Epstein-Barr virus-encoded small RNA, suggesting that this case could be categorized into HHV-8-associated solid lymphoma, a recently identified disease entity.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Cyclophosphamide; Disease Progression; Doxorubicin; Epstein-Barr Virus Infections; Fatal Outcome; Gastrointestinal Neoplasms; Herpesviridae Infections; Herpesvirus 4, Human; Herpesvirus 8, Human; HIV-1; Humans; Lamivudine; Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Male; Neoplasms, Second Primary; Prednisone; Ritonavir; Saquinavir; Sarcoma, Kaposi; Skin Neoplasms; Stavudine; Tumor Virus Infections; Vincristine