The overall goal of this study is to design a user-centered design app linked to a smart pill box for people living with HIV (PLWH) and evaluate its effects in a randomized controlled trial. The proposed trial is scientifically significant in representing a principled and systematic effort to test the efficacy of a smartphone intervention linked to a smart pill box for antiretroviral (ART) adherence in PLWH in the United States (US). Guided by a strong theoretical framework building on earlier user-centered design work and integrating a real-time monitoring device, this work has the potential to improve ART adherence in PLWH and have a sustainable public health impact.