In Perú, men who have sex with men (MSM) and transgender women (TW) suffer rates of HIV 50 times greater than the general population. MSM or TW sex workers (SWs) are at especially high risk. Daily oral pre-exposure prophylaxis (PrEP) effectively prevents HIV infection if patients adhere to a daily or on-demand regimen. Necessary levels of adoption and adherence require data-driven intervention strategies for these marginalized groups. We conducted qualitative content analysis of data obtained from focus groups (FGs) with MSM and TW SWs. Both groups expressed strong skepticism about the motives behind international drug trials, and the safety of participating in them. Important differences between MSM and TW groups’ beliefs about trustworthy information as well as community and public institutions also emerged. MSM SWs were less trusting of information from other MSM SWs, and preferred to receive information from institutional medical sources, while TGW SWs preferred to receive information from other TGW SWs. Successful strategies to encourage PrEP uptake and adherence must address the distrust patients feel towards international and institutional actors by providing patients with tailored, reliable information from local and community sources that they trust.