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There are 36.7 million people living with HIV, of whom 19.4 million (53%) live in eastern and southern Africa. Last year, 1.8 million people became newly infected, with 43% residing in eastern and southern Africa. South Africa has over 7 million people infected (20% of the global total), the largest number of infected people in any country. In 2016, 380,000 new infections occurred in South Africa, along with 180,000 AIDS-related deaths. Currently one of every 10 individuals are infected, and in some areas, one of every three young women are infected. By 2005, South Africa had the highest incidence in the world. This led to a vigorous response by the scientific community to study and advocate for a more intensive public health and governmental response. Drs. Quarraisha Abdool and Salim Abdool Karim responded by building the Centre of AIDS Programme of Research in South Africa (CAPRISA), one of the most respected research entities in the continent. They documented very high rates of infection in young women, described social patterns and risk factors of high transmission, identified mucosal factors associated with increased susceptibility, and implemented the first successful trial of Tenofovir microbicide, effective in decreasing acquisition of both HIV and HSV-2 in women. They implemented antiretroviral access programs responsible for a 29% decline in new infections in adults and a 56% decline in neonatal infections since 2010. Their efforts along with others have led to the largest number of people on antiretroviral therapy at 3.5 million people. Drs. Q. and S. Karim have demonstrated the scientific leadership that will be necessary to fully control the HIV pandemic in South Africa.