Ruth Gwandure earned her master of science degree in medicine (bioethics and law) from the University of the Witwatersrand, South Africa. Her research and consulting fields include bioethics, health law, environmental bioethics, research ethics, HIV and AIDS, ethics and law, clinical ethics, and HIV counselling and testing in schools. Calvin Gwandure has a PhD in psychology. He graduated from Nelson Mandela University, South Africa. His research and consulting fields include HIV and AIDS prevention, new HIV prevention technologies, HIV risk behavior, and group behavior. Clinical trials on HIV and AIDS prevention face challenges associated with infection of participants with HIV and sexually transmitted infections. Participants also experience adverse events associated with voluntary medical male circumcision and the use of microbicides and vaccines in clinical trials. The results obtained from clinical trials investigating the efficacy of microbicides and vaccines in preventing HIV infection are disappointing, but there is hope that one day a breakthrough could be made. Clinical trials on voluntary medical male circumcision and preexposure prophylaxis have shown positive results that warranted approval by the US Food and Drug Administration (FDA) and the World Health Organization (WHO). The major challenge experienced in new HIV prevention clinical trials that are underway and in approved interventions that are being scaled up apparently relates to HIV incidence that threatens the social value and scientific validity of the interventions. Paradoxically, the clinical trials and scale-up interventions have become the new sources of HIV infection although the hypothesized benefit to be realized in the end is conceptualized as outweighing the current risks involved.