People with HIV experience elevated levels of co-occurring psychosocial concerns, which can interfere with HIV-related self-care behaviors, such as medication adherence. We recently developed transdiagnostic, integrated cognitive-behavioral therapy and motivational interviewing psychotherapy to address interrelated psychosocial problems (syndemics) that can interfere with medication adherence and self-care among people with uncontrolled HIV (i.e., a detectable viral load). Through completion of a field trial that included development, clinical supervision, treatment, and administrative coordination of this project, we identified recommendations for engaging, retaining, and delivering transdiagnostic cognitive-behavioral therapy/motivational interviewing to individuals with HIV and experiencing psychosocial and structural barriers to mental and physical health. We describe these recommendations, which include (a) building the relationship; (b) addressing HIV in the context of syndemics; (c) attending to the impact of stigma on health; (d) being flexible in delivering the treatment; (e) managing emergent crises with relevant skill material; (f) tailoring the treatment to education, language, and sociocultural context; (g) implementing problem-solving skills for structural barriers; (h) scheduling flexibly and following up; (i) colocating mental health services and coordinating among providers; and (j) providing a comfortable and affirming physical space. In addition to describing these recommendations, we provide clinical examples and highlight empirical research to illustrate and support using these recommendations. (PsycINFO Database Record (c) 2020 APA, all rights reserved).