The HIV/AIDS pandemic continues to be a major global health problem. Despite significantly accelerated implementation of effective prevention and treatment tools to address HIV and AIDS, over 2 million new infections occurred in 2014. Sub-Saharan Africa remains the region most severely affected, bearing the burden of 66% of the HIV positive people in the world. In sub-Saharan Africa, nearly half of the 25.8 million people living with HIV are women. Given the scope of the epidemic, new biomedical tools to prevent HIV are essential. The most promising of these is a safe and effective HIV vaccine that provides durable protection, thus providing a realistic and cost-effective means of reversing HIV on a population level. It is highly unlikely that a global, sustainable solution to the AIDS pandemic will be economically or logistically feasible in the absence of a safe and effective HIV vaccine. Developing and delivering an AIDS vaccine for those most in need will represent a transformational scientific breakthrough and is in lock-step with USAIDâ€™s commitment to high-impact development through innovation. Parallel to this noble scientific endeavor supported by USAID since 2001 are concerted efforts to enhance human resources and infrastructure, while creating and nurturing an enabling policy environment and key partnerships in low- and lower middle-income countries that contribute to sustained capacity for science, research and health systems strengthening in the regions most affected by HIV/AIDS.