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Background: We set out to estimate, for the three geographical regions with the highest HIV prevalence, (sub-Saharan Africa [SSA], the Caribbean and the Greater Mekong sub-region of East Asia), the human resource and economic impact of HIV on the supply of education from 2008 to 2015, the target date for the achievement of Education For All (EFA), contrasting the continuation of access to care, support and Antiretroviral therapy (ART) to the scenario of universal access. Methodology/Principal Findings: A costed mathematical model of the impact of HIV and ART on teacher recruitment, mortality and absenteeism (Ed-SIDA) was run using best available data for 58 countries, and results aggregated by region. It was estimated that (1) The impact of HIV on teacher supply is sufficient to derail efforts to achieve EFA in several countries and universal access can mitigate this. (2) In SSA, the 2008 costs to education of HIV were about half of those estimated in 2002. Providing universal access for teachers in SSA is cost-effective on education returns alone and provides a return of $3.99 on the dollar. (3) The impacts on education in the hyperendemic countries in Southern Africa will continue to increase to 2015 from its 2008 level, already the highest in the world. (4) If treatment roll-out is successful, numbers of HIV positive teachers are set to increase in all the regions studied. Conclusions/Significance: The return on investing in care and support is also greater in those areas with highest impact. SSA requires increased investment in teacher support, testing and particularly ART if it is to achieve EFA. The situation for teachers in the Caribbean and East Asia is similar but on a smaller scale proportionate to the lower levels of infection and greater existing access to care and support. © 2012 Risley et al.