Dupilumab is an IgG4 human monoclonal antibody licensed for the treatment of moderate-to-severe atopic dermatitis. Despite evidence suggesting that T helper type two cytokines can modulate HIV-1 replication and anti-HIV-specific immune responses, impacting on viral reservoirs, HIV-positive patients under immunomodulating therapy have been excluded from clinical trials. We report a 47-year-old HIV-positive man with late-onset severe atopic dermatitis, treated with dupilumab and followed up for 27 months. Improvements in skin lesions and quality of life were observed after four months. Blood tests showed normalization of IgE levels, with the clinical condition remaining stable at a 27- month follow-up. We gathered 16 other cases reported in the literature of HIV-positive patients treated with dupilumab, with no, or few adverse reactions, for which it is unclear if dupilumab should be held accountable. With our case and literature review, we aim to shed light on dupilumab efficacy, safety, and tolerability among HIV-positive patients suffering from atopic dermatitis. In this regard, future research should focus on the effective role, underlying mechanisms, and efficacy of dupilumab in HIV-positive patients and HIV-positivity could be questioned as a valid exclusion criterion for clinical trials.