Background: Migrant sex workers are often highly marginalized and disproportionately experience health and social inequities, including high prevalence of HIV, sexually transmitted infections, and human rights violations. In recent years, research involving migrant sex workers has increased, yet many knowledge gaps remain regarding how best to protect research participant rights and welfare. Our objective was to identify key challenges and opportunities related to the responsible conduct of HIV research with migrant sex workers. Methods: Focus groups and interviews conducted with 33 female sex workers ≥18 years old at the Guatemala-Mexico border from June 2013-February 2014 were analyzed. Participants were recruited through community outreach by a local HIV prevention organization to sex work establishments such as bars, hotels, street corners, and truck stops. Results: Key themes influencing research engagement for migrant sex workers included researcher mistrust and fear related to research participation, rooted in the social isolation frequently faced by recent migrants; intersecting concerns related to immigration status, fear of criminalization, and compliance with sex work regulations; and perceived benefits and risks of HIV/STI testing for migrants (e.g., immigration implications, stigma) represent potential barriers and opportunities for the responsible conduct of research involving migrant sex workers. Conclusions: Results highlight the intersection between the human rights vulnerabilities of migrant sex workers and barriers to research participation, including social isolation of migrants and policy/legal barriers related to immigration and sex work. Findings illustrate the need for researchers to develop population-tailored procedures to address fears related to immigration and criminalization, and to reinforce positive and non-stigmatizing relationships with migrant sex workers. Community-led efforts to reduce stigma and foster community organization and supports for migrant sex workers are recommended, as are broader policy shifts that move away from punitive legal approaches towards approaches that safeguard and prioritize the human rights of migrant sex workers. © 2016 Goldenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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information processing Guatemala scientist HIV Infections Human immunodeficiency virus infection health care policy human social isolation immigration middle aged community Mexico Human immunodeficiency virus human rights interview Young Adult Humans migrant female prostitution stigma adult human experiment migration Sex Work Health Policy Transients and Migrants Focus Groups Fear pathophysiology social behavior