AbstractIn HIV hyperendemic sub-Saharan African communities, particularly in southern Africa, the likelihood of achieving the Sustainable Development Goal of ending the tuberculosis (TB) epidemic by 2030 is low, due to lack of cost-effective and practical interventions in population settings. We used one of Africa’s largest population-based prospective cohorts from rural KwaZulu-Natal Province, South Africa, to measure the spatial variations in the prevalence of recently-diagnosed TB disease, and to quantify the impact of community coverage of antiretroviral therapy (ART) on recently-diagnosed TB disease. We collected data on TB disease episodes from a population-based sample of 41,812 adult individuals between 2009 and 2015. Spatial clusters (‘hotspots’) of recently-diagnosed TB were identified using a space-time scan statistic. Multilevel logistic regression models were fitted to investigate the relationship between community ART coverage and recently-diagnosed TB. Spatial clusters of recently-diagnosed TB were identified in a region characterized by a high prevalence of HIV and population movement. Every percentage increase in ART coverage was associated with a 2% decrease in the odds of recently-diagnosed TB (aOR = 0.98, 95% CI:0.97–0.99). We identified for the first time the clear occurrence of recently-diagnosed TB hotspots, and quantified potential benefit of increased community ART coverage in lowering tuberculosis, highlighting the need to prioritize the expansion of such effective population interventions targeting high-risk areas.