Understanding the rise of HIV-associated Hodgkin Lymphoma despite HAART: the role of immune dysregulation (360G-Wellcome-200144_Z_15_Z)

HIV-associated Hodgkin Lymphoma (HIV-HL) is the second commonest non AIDS-defining HIV-associated malignancy and incidence is rising despite highly active antiretroviral therapy (HAART). Although intensive chemotherapy cures 80%, treatment toxicity is significant and prognosis for the remaining 20% poor. There is an urgent need for more effective, less toxic therapy, especially in poor nations where safe chemotherapy delivery is difficult. CD4+T cells coordinate the anti-tumor response but some are manipulated into supporting the lymphoma. Low HIV-HL incidence at low CD4 counts suggests CD4+T support is essential to HL survival. Additionally, low HIV-HL incidence at high CD4 counts (when immunosurveillance is strong) highlights their important anti-tumor role. Our preliminary data supports our hypothesis that the peak of HIV-HL at intermediate CD4 counts despite HAART relates to compromised immunosurveillance and a requirement for CD4+T support. Drawing on our group’s experience we will study a large cohort formed through international collaboration and aim to test this hypothesis and functionally characterise mechanisms involved. By targeting mechanisms protecting malignant cells we can increase effectiveness of current therapies and reduce dosage. Furthermore, this project may explain the rise of HIV-HL despite HAART and identify mechanisms limiting cell survival ex vivo which hold back study of this disease.