We report a case of a 43-year-old woman, affected by human immunodeficiency virus (HIV) and beta-thalassemia major (beta-TM), adequately treated with antiretroviral and transfusion-chelation therapy, that develops progressive right ventricular dysfunction due to severe pulmonary arterial hypertension (PAH), in absence of symptoms. The existence of both HIV and beta-TM cardiomiopathy has recently been reported, but how these two diseases have a "competition of guilt" for creating PAH is still to be understood. The main physiopathological principles regarding HIV and beta-TM associated PAH are reviewed. The possible interplay between these two different pathologies is discussed.