Atopic dermatitis (AD) is a chronic immune-mediated inflammatory disease typical of childhood that can also affect adults. AD is clinically characterized by intensely pruritic eczematous lesions. The burden of this disease and its impact on quality of life are often substantial. Dupilumab is a fully humanized monoclonal antibody against interleukin 4 (IL-4) receptor α, capable of blocking IL-4 and IL-13 signaling. This novel therapy represents the first biologic approved for the treatment of moderate to severe AD. Our report describes the case of a 39-year-old adult patient affected by severe chronic AD with associated allergic and viral comorbidities for whom conventional systemic therapies proved ineffective or contraindicated. The main source of interest in this case is hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection because, to our knowledge, this is the first case of an adult atopic patient treated with dupilumab in the simultaneous presence of these comorbidities. Regarding coinfections, the patient was on antiretroviral therapy for HBV and HIV before starting dupilumab. Efficacy and safety data after 24 weeks of therapy are reported in detail.