The evaluation of new therapies to achieve an antiretroviral therapy (ART)-free remission of HIV infection will require demonstration of efficacy through ART interruption studies. However, there are concerns about stopping ART, including patient safety, selection of HIV drug resistance and increased risk for HIV transmission. In this article, we highlight the importance of identifying biomarkers of ART-free remission for cure research and present an updated approach to treatment interruption that should identify predictive markers while minimizing negative consequences for participants. The proposed approach, termed an intensely monitored antiretroviral pause (MAP), has the potential to accelerate progress towards an HIV cure.