The pathogenesis of HIV infection, particularly the development of immunodeficiency, remains incompletely understood. Both innate and adaptive immune responses are raised but appear insufficient or too late to eliminate the virus. The innate immune response plays a crucial role in HIV pathogenesis, contributing to viral transmission, immune-mediated T cell death, chronic immune activation, and defense against established infection. Key mechanisms include the recognition of HIV-derived pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and retinoid acid-inducible gene (RIG)-like receptors (RLRs). TLR7/8 activation by uridine-rich ssRNA from HIV's long terminal repeat (LTR) and gp120 binding to DC-SIGN are the only confirmed direct links between HIV and innate PRRs. Innate immune activation is also driven by PAMPs from opportunistic pathogens and translocated bacteria, which activate TLRs. The dual role of innate immune activation in HIV infection involves both antiviral and pathological effects, with type I interferons (IFNs) having both beneficial and detrimental roles. The balance between proinflammatory Th17 cells and regulatory T cells (Tregs) is altered in HIV infection, contributing to immune dysregulation. The complex interplay between HIV and the innate immune system highlights the need for further research to understand the full spectrum of HIV pathogenesis.The pathogenesis of HIV infection, particularly the development of immunodeficiency, remains incompletely understood. Both innate and adaptive immune responses are raised but appear insufficient or too late to eliminate the virus. The innate immune response plays a crucial role in HIV pathogenesis, contributing to viral transmission, immune-mediated T cell death, chronic immune activation, and defense against established infection. Key mechanisms include the recognition of HIV-derived pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and retinoid acid-inducible gene (RIG)-like receptors (RLRs). TLR7/8 activation by uridine-rich ssRNA from HIV's long terminal repeat (LTR) and gp120 binding to DC-SIGN are the only confirmed direct links between HIV and innate PRRs. Innate immune activation is also driven by PAMPs from opportunistic pathogens and translocated bacteria, which activate TLRs. The dual role of innate immune activation in HIV infection involves both antiviral and pathological effects, with type I interferons (IFNs) having both beneficial and detrimental roles. The balance between proinflammatory Th17 cells and regulatory T cells (Tregs) is altered in HIV infection, contributing to immune dysregulation. The complex interplay between HIV and the innate immune system highlights the need for further research to understand the full spectrum of HIV pathogenesis.