Explanatory models describe individuals’ perceptions of their illness experiences, which can guide culturally relevant care. We constructed an explanatory model of the experience of living with human immunodeficiency virus (HIV) in the Dominican Republic. Following qualitative descriptive methodology, we conducted interviews in Spanish using a semi-structured interview guide developed using Kleinman’s explanatory model framework. Two bilingual researchers coded interview transcripts following conventional content analysis. We used deductive codes from Kleinman’s framework and inductive codes external to the framework to construct the codebook. We arranged codes by shared meaning into categories and constructed themes that reflected shared findings from inductive categories and deductive codes. Twenty-six persons living with HIV participated. They provided rich descriptions of their experiences represented by four cross-cutting themes, which informed the explanatory model. By incorporating this in-depth understanding of patients’ illness experiences into care delivery, nurses can cultivate culturally meaningful and trusting patient-centered partnerships that improve health.