Since the beginning of the HIV/AIDS epidemy in the eighties, hundreds of phase I human immunization studies were performed, however, only nine tested efficacy in phase IIb/III clinical trials. While immunogens for SARS-CoV-2 did move along the development and clinical trial pipeline at unprecedent speed, two HIV immunization vaccine trials, started in 2016 and 2017, did meet non-efficacy criteria at the interim analysis and were thus, halted by the Data and Safety Monitoring Boards. The challenges in the quest to develop a safe, effective and durable HIV vaccine are unchanged. However, as research on HIV vaccine discovery moves forward there are many new tools and platform technologies to iterate vaccine strategies faster. Among these, there is a growing interest to conduct experimental medicine approaches where product development is directly informed by human data at an early stage of product development.