Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a major public health concern in sub-Saharan Africa. Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. HIV-HBV co-infection is common we report the case of an association of cerebral toxoplasmosis with mediastinal lymph node tuberculosis in a patient with HIV-HBV co-infection. The diagnosis of this extra-pulmonary tuberculosis and cerebral toxoplasmosis was presumptive and was made probable by the test therapies that were effective. Concomitant treatment of these two opportunistic infections with antiretroviral therapy resulted in severe drug hepatitis that was probably favored by hepatitis B that HIV infection would have worsened. The choice of effective and less toxic antiretroviral triple therapy was difficult in the absence of recommendations for such combinations.