Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China with a growing number of circulating recombinant forms due to increasing human contact, particularly in large urban centers, tourist locations and in sites of common infrastructure. A vaccine countering CRF01_AE is a priority for the region. An Asia HIV vaccine against expanding B/E or BCE recombinant forms should be actively pursued. A major challenge that remains is the conduct of efficacy trials in heterosexual populations in this region. Men who have sex with men represent the main target population for future efficacy trials in Asia. Coupling HIV vaccines with other prevention modalities in efficacy trials might also be envisaged. These new avenues will only be made possible through the conduct of large-scale efficacy trials, interdisciplinary teams, international collaborations, and strong political and community commitments.