The general ethical principles that govern all clinical research apply to vaccine trials, and there are a number of international statements on medical ethics that apply. It is fundamental that participation in trials must be voluntary and based on individual informed consent.

The principal difference between preventive vaccine trials and HIV therapeutic trials is that because participants might otherwise have a normal life expectancy and a low level of disability, the level of potentially acceptable risk is much lower.

In the case of HIV preventive vaccines, much of the discussion of ethics of trials has been driven by perceived and actual disparities of power between those at high risk of HIV and those carrying out the research, and between Western countries and multinational companies and communities in developing countries. There is an obvious danger of exploitation, if benefits and risks from research are not evenly shared. There is also a danger that if governments and international agencies are over-protective, the effort will be stalled.