Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap is a severe and potentially life-threatening condition characterized by widespread blistering and necrosis of the skin and mucous membranes. This condition is often triggered by a delayed-type hypersensitivity reaction, which can be caused by certain medications or infections. In particular, individuals with HIV/AIDS are at a higher risk of developing hypersensitivity reactions, including SJS and TEN, due to their compromised immune system. Sulfadoxine-pyrimethamine (SP), an antibiotic commonly used to treat malaria, has also been associated with an increased risk of hypersensitivity reactions, including SJS and TEN. A recent case study illustrates the potential dangers of self-medication with SP in individuals with HIV/AIDS. A 20-year-old female with HIV/AIDS, who was not adhering to her antiretroviral therapy, developed fever, body pain, and skin blisters on her face, neck, trunk, and perineum after taking SP for malaria. The skin involvement was significant, covering 23% of her total body surface area (TBSA). The patient's condition was assessed using the Naranjo Adverse Drug Reaction Scale, which suggested a possible association between SP and the development of SJS/TEN overlap. Fortunately, the patient received prompt and conservative treatment, including fluids, antimicrobials, nutrition, and wound care, and made a complete recovery. This case highlights the importance of educating HIV patients about the risks of self-medication with antibiotics like SP and the need for careful monitoring and management of potential adverse drug reactions. The medicine regulatory authority and healthcare professionals must work together to raise awareness about the dangers of self-medication and to prevent similar cases of SJS/TEN overlap in the future. Link: https://pubmed.ncbi.nlm.nih.gov/40475371/