Long-term evolution of HIV because of noncompliance and nonadherence to antiretroviral therapy favors the occurrence of difficult to treat HIV-related malignancies. We present the case of a female patient in “the pediatric cohort” registered at the Iaşi Regional HIV/AIDS Center since year 2000, now with stage C3 AIDS. In 2014, a Burkitt lymphoma was pathologically confirmed, and chemotherapy was initiated as recommended by the hematologist. The clinical course was characterized by multiple complications: hematologic and hepatic toxicities, opportunistic infections and depressive episodes. Highly active antiretroviral therapy associated with sustained psychological support resulted in stabilization of the patient's clinical course (lower HIV viral load and higher CD4 lymphocyte cell counts), anticancer therapy being better tolerated. Currently, patient’s clinical-biological status is quasi-normal. The depressive episodes in this HIV-positive cancer patient undergoing chemotherapy contributed to her non-adherence and non-compliance to treatment, with serious consequences both on clinical and viroimmunological status. Therapeutic strategy in this patient with AIDS and Burkitt lymphoma raised management difficulties as both the drug interactions and cumulative adverse effects had to be considered. Multidisciplinary collaboration and especially psychological intervention are essential for creating a functional team, effective communication being key to achieving long-term adherence to treatment and diagnosis acceptance.