**5.3. HAART and other medication that cause bone marrow changes**

Introduction to highly active antiretroviral therapy (HAART) has resulted in a highly signifi‐ cant decline in mortality [67]. However, some of these drugs frequently cause haematologic toxicity. Several studies have shown that zidovudine and dideoxycytidine inhibit erythroid colony forming units (CFU-E) that are needed for erythroid formation and granulocyte macrophage colony forming units that is important for granulocyte formation [68]. Leucopenia can be seen in HIV patients treated with Ganciclovir. Pyrimethamine and sulfadiazine used in the treatment of toxoplasmosis cause leucopenia and thrombocytopenia. Chemotherapeutic agents used in the treatment of malignancies, especially lymphoma result in myelosuppression which is often dose limiting. Alpha interferon used in the treatment of Kaposi sarcoma in HIV patient is frequently associated with haematologic toxicity [69].

### **5.4. Lymphoma in HIV disease**

Lymphoma is a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes [37]. Lymphadenopathy or enlargement of the lymph nodes is the main clinical feature. It can be subdivided into Hodgkin's lymphoma and non-Hodgkin's lymphoma.

Patients with HIV disease have an increased incidence of lymphoma as compared to general population, especially diffuse non-Hodgkin's lymphoma subtype [70]. This is often of high grade lymphoma and mostly of B cell origin [70, 71]. The increased risk of lymphoma appears to be related to many factors, which are mainly related to a variety of genetic lesions, including infection by Epstein-Barr virus (EBV), c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 mutations/deletions [72]. The malignant lymphoma, probably arises as a monoclonal outgrowth from a pool of proliferating B lymphocytes, which have been stimulated by the infective agents such as EBV and CMV.These opportunistic infections contribute to the pathogenesis of lymphoma more seen in HIV infection. Lymphoma in HIV patients tends to metastasize to brain or spread extranodal [73]. The relapse rate is high and overall patients will have a poor prognosis. However, with the introduction of HAART treatment, the risk of lymphoma has decreased and the clinical outcome improved [73].
