Researchers working in 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 tissue cultures, or tried out in mathematical models and computer simulations. Ideas are refined, and from the best approaches an experimental product is developed.
Preclinical testing is done to see if the product is safe in animals, and whether it may be effective 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 become infected with 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. Ultimately we have to move forward into human studies, called clinical trials.
Phases of testing
Studies in human volunteers come in 3 main steps, or phases. If a vaccine or other product is approved a 4th phase for follow-up testing is sometimes added.
- 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 (often hundreds) of volunteers. The purpose of phase 2 studies is usually to understand even more about the safety of the product and any immune response 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.
In phase 1 and many phase 2 clinical studies evaluating HIV vaccine and other prevention products[c1] , we are not testing to see if a product protects anyone against HIV and AIDS. We are only testing how the body responds to the products. To see if a product actually protects against HIV and 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 (sometimes involving thousands of participants), but smaller than a phase 3 study.
- Phase 3 studies involve several thousand volunteers who are considered at risk for HIV infection because of their sexual behavior, drug use, or because they live in a region where HIV impacts many people, such as sub-Saharan Africa or parts of Asia. They are followed over time to determine if the study product actually works to prevent HIV infection. In HIV vaccine [ARF2] trials, the follow-up time is often 3-5 years.
- Phase 4 studies are sometimes done after a product is licensed and is being used. This phase is usually called a “post-marketing study.” In this type of study, the people who make the product want further information about it (such as unexpected side-effects) when it is given to more people in their everyday lives, rather than in the controlled conditions of a clinical trial.
The process described above is the most simplified and streamlined. Vaccine and other prevention products’ development often works that way, but there can be more to it. For example, after a product is tested in a phase 1 or 2 trial, it may be re-made in a slightly different way, which would mean that it has to go back to Phase 1 again. Or, instead of a single new vaccine product being tested, researchers may invent a new vaccine strategy using new combinations of vaccines, or new ways of giving the injections. Some studies may not involve new products at all, but are done to learn more about a certain part of the immune system or how the body works. In all cases, study volunteers play a crucial role. Progress toward finding effective prevention methods and ultimately a safe and effective vaccine could not be made without them.