Human Immunodeficiency Virus (HIV) significantly impacts skin structure, immune responses, and the microbiome, contributing to diverse dermatological conditions. The epidermis, a key physical and immunological barrier, undergoes structural changes such as hyperplasia and inflammatory infiltrates. Skin adnexal structures like hair follicles also play a role in immune modulation but are affected by HIV-related disruptions. Innate and adaptive immune systems are compromised due to CD4+ T-cell depletion, cytokine imbalances, and altered immune regulation, leading to conditions such as hypersensitivity and inflammatory dermatoses. The skin microbiome in HIV patients shows distinct shifts, including reduced Cutibacterium species and increased opportunistic microbes, independent of CD4+ levels. Age, sex, and environmental stressors exacerbate these changes, with women exhibiting stronger immune responses but higher risks of autoimmune diseases and aging men experiencing accelerated immunosenescence. Understanding these interconnected alterations is essential for developing targeted therapies to manage skin complications and improve the overall health of HIV patients.