Host response to the human immune deficiency virus (HIV) involves both the innate and adaptive immune systems. As part of the innate immune system, the killer cell immunoglobulin-like receptors (KIRs) found on natural killer cells and some T-lymphocytes are genetically diverse and play key functions in the host response against viral pathogens. In the last decade, there has been substantial growth in sequencing technologies and bioinformatics capacity to understand human host genetics, including KIR. However, there is limited literature on how the KIR diversity informs the perspectives on HIV disease states in understudied African settings. A better understanding of the effects of KIRs on the host’s immune response to HIV in African settings is essential to inform strategies to develop more effective therapies and vaccines to improve health among people living with HIV (PLWH). In this paper, we review KIR diversity, the role of KIR immunogenetic variation in the human host response to HIV, discuss current perspectives on the studies to assess the relationship between KIR diversity and the HIV disease continuum, and suggest future research prospects.