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BackgroundSexual minority men are disproportionately affected by HIV. Medical advances in HIV treatment have extended life expectancy, and as this group ages, medical and psychological challenges become more prominent. Older people with HIV experience a higher incidence of cancer and other comorbidities; these burdens along with sexual minority stress can strain coping resources and diminish health-related quality of life. Interventions such as cognitive behavioral stress and self-management (CBSM) can mitigate some of this burden; however, no manualized, eHealth-based interventions have focused on the unique needs of sexual minority men living with HIV and cancer. ObjectiveThis study aims to refine and finalize a web-based, CBSM-based intervention to meet the unique needs of this population, including sexual health, comanagement of 2 chronic conditions, and coping with sexual minority stress. MethodsThis mixed methods study used a previously completed qualitative phase (n=6) to inform the development of a web-based platform and intervention called SmartManage. The pilot phase study (n=50) involved randomization (1:1) into either 10 sessions of adapted CBSM or an attention control health promotion. Both conditions used the SmartManage platform, a web-based eHealth program designed to deliver CBSM and health promotion content and host live groups. Feasibility and acceptability (eg, rates of participant engagement and retention) were the primary outcomes. ResultsParticipant-related activities are expected to be completed by November 2022, and results are expected to be submitted for publication by February 2023. ConclusionsWe hypothesize that participants would find the intervention acceptable (compared with engagement and retention rates observed in similar CBSM studies). We also hypothesize that participants receiving the SmartManage intervention would have reduced symptom burden and improved health-related quality of life before and after treatment compared with those who do not. International Registered Report Identifier (IRRID)DERR1-10.2196/37822