Developing and Testing Theories
Scientists working at universities, pharmaceutical or biotechnology companies, and research centers are constantly testing out theories for how to make new or better HIV vaccines and prevention products. Initially, ideas can be tested in labs, or tried out in mathematical models and computer simulations. Ideas are refined, and from the best approaches an experimental vaccine is developed.
Preclinical testing is done to see if the product is safe in animals, and whether it may be appropriate to continue studies in people. The most common animals that are used in preclinical tests of HIV prevention products are mice, rabbits, and rhesus macaque monkeys. Even if a product looks safe in animals, the same may not be true in people. And no matter how much we learn in preclinical tests, only people can get HIV — human immunodeficiency virus, the virus that causes AIDS. Since animals’ immune systems are different from those of people, the only way to prove a new product's safety and effectiveness in people is to test it in people. If the product looks pomising in animals, we have to make the decision about whether to move forward into human studies, called clinical trials.
Phases of Testing
Studies in human volunteers come in 3 main steps, or phases.
Phase 1 studies involve a small number of healthy volunteers; “healthy” in the context of HIV prevention studies means HIV-negative and free of any significant medical problems. These volunteers are also at low risk for HIV infection. The main purpose of a Phase 1 study is to test the safety of the product, and to see if it causes an immune response.
Phase 2 studies involve larger numbers (hundreds) of volunteers. The purpose of Phase 2 studies is usually to understand more about the safety of the product and any immune responses it causes by studying it in more people. Questions about the right dose and the scheduling of the doses can usually be further sorted out here. As studies get larger, the diversity of participants can also increase.
Phase 2b and 3 studies involve several thousand volunteers who are considered at risk for acquiring HIV because of their sexual behavior or drug use. They are followed over time to determine if the study product actually works to prevent HIV infection. In HIV vaccine trials, the follow-up time is often 3-5 years.
In Phase 1 and Phase 2 clinical studies, we are not testing to see if a product protects anyone against HIV/AIDS. We are only testing how the body responds to the products. To see if a product actually protects against HIV/AIDS, an efficacy study is conducted, which is often called a Phase 3 study. However, sometimes the HVTN may use a special step called a Phase 2b trial. A Phase 2b trial is designed to test the concept of whether a product idea should advance to a Phase 3 or be scrapped. It is a quicker way to test the promise of an HIV study product. Phase 2b trials are larger than Phase 2 (involving thousands of participants), but smaller than a Phase 3 study.