Clinical Research on HIV/AIDS Vaccines

2
* whole-inactivated virus vaccine: HIV that has been inactivated by chemicals, irradiation
or other means so it is not infectious.
* live-attenuated virus vaccine: live HIV from which one or more apparent diseasepromoting genes of the virus have been deleted.
Clinical Trials Background
After an experimental vaccine performs well in preclinical safety and immunogenicity tests, it
must successfully complete three stages of testing in people before development into a licensed
product.
A Phase I trial is the first setting in which an experimental HIV vaccine is given to people. Such
a trial enrolls about 20 to 80 non-HIV-infected volunteers at apparent low risk of HIV infection.
A Phase I trial primarily seeks information on safety, usually assessing any vaccine-related side
effects by comparing the vaccine with an inactive placebo or control that looks like the test
product. A Phase I trial also can provide data on the vaccine's immunogenicity, including the
dose and administration schedule required to achieve optimal immune responses. If the vaccine
elicits neutralizing antibodies, scientists can study how these react against HIV strains from the
same or other clades to determine the potential breadth of protection. A Phase I trial may last one
to two years.
Once Phase I trials show that the experimental HIV vaccine is well-tolerated, it can advance into
Phase II trials. These trials enroll more people, up to a few hundred, and often include some
volunteers at higher risk for acquiring HIV. Researchers gather data about safety and immune
responses, asking more sophisticated questions that such larger trials allow. Optimally, the trials
are randomized and double-blind, meaning that volunteers are assigned at random to a study
group and that neither the health care workers nor the patients know what preparations the
patients receive. Phase II trials usually last one to two years.
The most promising candidate vaccines move into Phase III or efficacy trials, enrolling large
numbers of non-HIV-infected people at high risk for exposure to the virus. A Phase III trial
usually is designed to ensure the collection of enough data on safety and effectiveness to support
a license application, if warranted. The vaccine may be tested against a placebo or a vaccine
such as hepatitis B of known potential benefit to the study population. An efficacy trial can
involve thousands of volunteers and therefore takes much longer, at least four years, to complete.
Clinical Trials of Preventive Vaccines
In August 1987, NIAID opened the first clinical trial of an experimental HIV vaccine at the NIH
Clinical Center in Bethesda, Md. This safety trial eventually enrolled 138 non-infected healthy
volunteers. The gpl60 subunit candidate vaccine tested caused no serious adverse effects.