HIV specifically infects cells expressing the CD4 surface glycoprotein, primarily CD4⁺ Helper T lymphocytes (T helper cells), along with macrophages and dendritic cells. The HIV envelope protein gp120 binds CD4 along with a co-receptor (CCR5 or CXCR4). Progressive depletion of CD4⁺ T cells (from ~1,000 cells/μL to <200 cells/μL) cripples cell-mediated immunity, leading to AIDS and susceptibility to opportunistic infections.