Understanding the role of host genetics in modulating susceptibility to viral pathogens such as HIV is crucial for developing targeted prevention and treatment strategies. This review delves into the intricate interplay between host genetic factors and immune responses in the context of infectious diseases, with a particular focus on HIV. Recent advancements in immunogenetics have highlighted the significant impact of host genetic variation on susceptibility to HIV infection and disease progression. Genetic polymorphisms within key immune response genes, including those involved in antigen presentation, T cell activation, and cytokine signaling, have been implicated in shaping individual susceptibility to HIV acquisition and progression to AIDS. Furthermore, the influence of host genetic factors extends to antiretroviral therapy (ART) outcomes, with certain genetic variants influencing drug metabolism and treatment efficacy. Beyond individual gene variants, genome-wide association studies (GWAS) have identified complex genetic signatures associated with HIV susceptibility and progression, underscoring the multifactorial nature of host-virus interactions. Moreover, epigenetic mechanisms, such as DNA methylation and histone modifications, may further modulate host immune responses to HIV infection. However, unraveling the intricate genetic architecture underlying HIV susceptibility and immune response heterogeneity remains a daunting challenge. Integrative approaches combining genomics, transcriptomics, and functional studies are essential for deciphering the complex networks of host-virus interactions