This study investigates baseline differences in couples enrolled in the "It Takes Two" HIV prevention intervention for transgender women and their partners, comparing in-person participation pre-COVID-19 and digital participation during the pandemic. Among 52 couples (40% in-person, 60% digital), bivariate analyses revealed that in-person participants were more likely to be African American, have cisgender male partners, report higher unemployment, incarceration histories, greater relationship stigma, and lower relationship quality. The findings highlight the limitations of digital modalities in engaging transgender women of color and those with structural vulnerabilities. The study emphasizes that reliance on digital methods in HIV research jeopardizes the inclusion of those lacking technological access and literacy, especially communities disproportionately impacted by HIV. Researchers must incorporate hybrid or in-person options and engage communities to ensure equity and inclusion, thus overcoming barriers and ensuring comprehensive population reach in HIV prevention studies.