Clinical trials answer specific questions about a preventive vaccine by comparing one group of people that receives the vaccine with another that receives a placebo—a substance that has all of the ingredients of the vaccine preparation except its active agent. To avoid biasing results, nobody knows who precisely has received which preparation until the trial has been completed. All volunteers must be free of HIV infection at the start of any such trial.

• Phase I: Assess the safety of the vaccine in a few dozen healthy people. They may also assess the immunogenicity of the vaccine, or its basic ability to generate an immune response.
  
• Phase II: Assesses the safety and the immunogenicity of a vaccine in a larger group (numbering in the hundreds) of people. A version of this trial, known as the Phase IIb or test of concept trial, may also begin to examine the candidate vaccine’s efficacy—its ability to protect people from HIV.
  
• Phase III: This is the true test of a vaccine’s efficacy. It usually involves thousands of people, and can take up to five years to complete. Volunteers are typically recruited from populations known to be at high risk of HIV infection, but are counseled throughout the trial about the importance of HIV prevention.

Once a vaccine has been approved, ongoing studies sometimes referred to as Phase IV trials ask additional questions about the safety and effectiveness of a vaccine when it is put into general use in a population.