Adolescents and young people represent a growing proportion of people living with HIV (AYAHIV), and there is an urgent need to design, implement, and test interventions that retain AYAHIV in care. Using a human-centered design (HCD) approach, we codesigned CombinADO, an intervention to promote HIV viral suppression and improve antiretroviral therapy (ART) adherence and retention in care among AYAHIV in Nampula, Mozambique. The HCD process involves formative design research with AYAHIV, health care providers, parents/caretakers, and experts in adolescent HIV; synthesis of findings to generate action-oriented insights; ideation and prototyping of intervention components; and a pilot study to assess feasibility, acceptability, and uptake of intervention components. CombinADO promotes ART adherence and retention in care by fostering peer connectedness and belonging, providing accessible medical knowledge, demystifying and destigmatizing HIV, and cultivating a sense of hope among AYAHIV. Successful prototypes included a media campaign to reduce HIV stigma and increase medical literacy; a toolkit to help providers communicate and address the unique needs of AYAHIV clients; peer-support groups to improve medical literacy, empower youth, and provide positive role models for people living with HIV; support groups for parents/caregivers; and discreet pill containers to promote adherence outside the home. In the next phase, the effectiveness of CombinaADO on retention in care, ART adherence, and viral suppression will be evaluated using a cluster-randomized control trial. We demonstrate the utility of using HCD to cocreate a multicomponent intervention to retain AYAHIV in care. We also discuss how the HCD methodology enriches participatory methods and community engagement. This is then illustrated by the youth-driven intervention development of CombinADO by fostering youth empowerment, addressing power imbalances between youth and adult stakeholders, and ensuring that language and content remain adolescent-friendly.