Objective Adolescents have had very limited access to research on biomedical prevention interventions despite high rates of HIV acquisition. One concern is that adolescents are a vulnerable population, and trials carry a possibility of harm, requiring investigators to take additional precautions. Of particular concern is preventive misconception, or the overestimation of personal protection that is afforded by enrolment in a prevention intervention trial.

Methods As part of a larger study of preventive misconception in adolescent HIV vaccine trials, we interviewed 33 male and female 16–19-year-olds who have sex with men. Participants underwent a simulated HIV vaccine trial consent process, and then completed a semistructured interview about their understanding and opinions related to enrolment in a HIV vaccine trial. A grounded theory analysis looked for shared concepts, and focused on the content and process of adolescent participants’ understanding of HIV vaccination and the components of preventive misconception, including experiment, placebo and randomisation.

Results Across interviews, adolescents demonstrated active processing of information, in which they questioned the interviewer, verbally worked out their answers based upon information provided, and corrected themselves. We observed a wide variety of understanding of research concepts. While most understood experiment and placebo, fewer understood randomisation. All understood the need for safer sex even if they did not understand the more basic concepts.

Conclusions Education about basic concepts related to clinical trials, time to absorb materials and assessment of understanding may be necessary in future biomedical prevention trials.