Brentuximab vedotin (BV) is a drug that has improved outcomes in classical Hodgkin lymphoma (cHL). However, its safety and efficacy in patients living with HIV who present with severe liver failure and life-threating cytopenias is unclear. Here, we describe the case of a woman living with HIV diagnosed with cHL and how she recovered from a hemoglobin nadir of 24 g/L despite declining transfusion support and a bilirubin peak of 417.24 µmol/L, eventually achieving a complete response with a BV-based therapy. Studies are needed to determine the safety and efficacy of BV in patients excluded from the pivotal trials.