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Background People with HIV (PWH) from racial and ethnic minority groups in the United States (US) face a high risk for severe COVID-19 outcomes and have low uptake of the COVID-19 vaccine primary series and booster doses. This study aims to provide insights into barriers and facilitators to vaccination and identify strategies to increase vaccine trust and uptake in these populations. Methods Between November and December 2022, we conducted qualitative interviews with 24 vaccinated and unvaccinated adult PWH who self-identified as Hispanic/Latinx, Black/African American, or Haitian, and were clients of the Miami-Dade County Ryan White HIV/AIDS Program in Florida, US. Data were analyzed using deductive thematic analysis. Results Main barriers to vaccine uptake reported by participants included low or no perception of COVID-19 risk, concerns about safety and efficacy related to HIV status, mistrust of COVID-19 vaccines, general vaccine hesitancy, negative experiences and advice against vaccination within social networks, lack of provider recommendation, and exposure to negative messaging and misinformation about vaccines. Facilitators included perceived risk, awareness of the vaccines’ protective benefits for HIV-immunocompromised individuals and reducing transmission, encouragement and role modeling within social networks, provider recommendation, and exposure to accurate information from reputable sources. Some recommended strategies to increase uptake and trust in vaccines included incorporating vaccination into routine HIV care, leveraging peers with HIV, tailoring vaccine information and messaging, and partnering with trusted individuals for outreach. Conclusion Vaccination efforts for PWH should prioritize addressing specific barriers and concerns related to their HIV status and tailoring strategies to meet their needs.