BackgroundThe HIV/AIDS pandemic has had a very devastating impact at a global level, with the Eastern and Southern African region being the hardest hit. The considerable geographical variation in the pandemic means varying impact of the disease in different settings, requiring differentiated interventions. While information on the prevalence of HIV at regional and national levels is readily available, the burden of the disease at smaller area levels, where health services are organized and delivered, is not well documented. This affects the targeting of HIV resources. There is need for studies to estimate HIV prevalence at appropriate levels to improve HIV related planning and resource allocation. MethodsWe estimated the district level prevalence of HIV using Small-Area Estimation (SAE) technique by utilizing the 2016 Zambia Population-Based HIV Impact Assessment Survey (ZAMPHIA) data and auxiliary data from the 2010 Zambian Census of Population and Housing and the HIV sentinel surveillance data from selected antenatal care clinics (ANC). SAE Models were fitted in R Programming to ascertain the best HIV predicting model. We then used the Fay-Herriot (FH) model to obtain weighted, more precise and reliable HIV prevalence for all the districts.ResultsThe results revealed variations in the district HIV prevalence in Zambia, with the prevalence ranging from as low as 4.2% to as high as 23.5%. Approximately 35% of the districts (n=26) had HIV prevalence above the national average, with one district having almost twice as much prevalence as the national level. Some rural districts have very high HIV prevalence rates. ConclusionsHIV prevalence in Zambian districts is driven by population mobility Districts located near international borders, along the main transit routes and adjacent to other districts with very high prevalence, tend to have high HIV prevalence. The variations in the burden of HIV across districts in Zambia points to the need for a differentiated approaches in HIV programming in Zambia. HIV resources need to be prioritized towards districts with high population mobility.