Preventive methods for HIV are the one of the most urgent global public health needs. However, obtaining reliable information on the clinical utility of novel preventive methods requires enrolment of high-risk individuals. This thesis addresses the challenges of enrolling these populations using a novel systematic review methodology. It then discusses the implications of participants requests for improved ethical treatment in clinical trials. One novel method in clinical trials has been the use of Pre-Exposure Prophylaxis (PREP) with the antiretroviral drug tenofovir. The trials have however, been marred with criticism by activist groups, citing ethical concerns and a lack of community involvement. This opposition and media coverage has stopped the progress of two PREP trials, in Cambodia and Cameroon, and threaten the stability of planned and recruiting trials of intravenous drug users in Thailand and other developing nations. The issues raised by activists, academics, and the trialist community display the dissonance in communication between these stakeholders and the need for mutual understanding of values. Without effectively engaging all stakeholder groups, these differences threaten to undermine the progress of prevention trials and ultimately affect the most important stakeholders, the at-risk individuals themselves.