Clinical Trials of HIV Vaccines
Experimental vaccines are first tested in laboratory and animal studies for safety
and immunogenicity. If the results are favorable, a vaccine must successfully complete
several phases of testing in people before it can gain Food and Drug Administration
(FDA) approval for licensing and marketing to the public. All the phases conduct
randomized, controlled, and double-blinded studies. These studies compare the safety
and effectiveness of the vaccine to an inactive placebo or a control that may be
another licensed vaccine of potential benefit to the study population, such as hepatitis
Phases of Clinical Trials
A Phase I trial is the first setting in which an experimental HIV vaccine is given
to people. The trial, which can last up to 2 years, may enroll between 20 to 100
HIV-uninfected volunteers at low risk for HIV infection. A Phase I trial primarily
seeks information on safety, particularly looking for any vaccine-related side effects.
The trial can also provide data on the dose and administration schedule needed to
achieve the optimal immune responses. If the vaccine elicits neutralizing antibodies
or cytotoxic T lymphocytes (CTLs), scientists can study whether these responses
are broadly protective against a wide variety of HIV strains that scientists refer
to as subtypes or clades.
Once Phase I trials show the experimental HIV vaccine is safe, well tolerated, and
appears promising, it can advance into Phase II. These trials, which can last longer
than 2 years, enroll between 100 to 300 volunteers at high and low risk for acquiring
HIV. In these trials researchers gather more data on safety and immunogenicity.
Investigators supported by NIAID also are developing designs for intermediate
trials that can provide preliminary answers about a candidate vaccine's efficacy
and determine if the vaccine candidate should move forward into large Phase III,
or efficacy, trials. A Phase IIb trial, also known as a "proof-of-concept" trial,
is smaller, requiring 2,000 to 5,000 volunteers, is less expensive than Phase III
trials and may provide clues about the immune responses that can protect against
The most promising vaccine candidates move into Phase III, enrolling 10,000 or more
HIV-uninfected people at high risk for exposure to the virus. A Phase III trial,
which can last up to 4 years, is typically designed to ensure enough data are collected
on safety and effectiveness to support a license application to FDA.
Clinical Trials of Preventive HIV Vaccines
Currently, there are no approved preventive vaccines for HIV infection. Since the
first HIV vaccine trial opened in 1987, researchers have studied more than 50 different
preventive vaccine candidates in more than 100 NIAID-funded clinical trials.
The first HIV vaccine clinical trial opened in August 1987 at the National Institutes
of Health Clinical Center in Bethesda, Maryland. This Phase I trial enrolled 138
healthy, uninfected volunteers. The gp160 subunit candidate vaccine tested caused
no serious adverse effects. Six months later, the NIAID AIDS Vaccine Evaluation
Group (AVEG), the first U.S. cooperative HIV vaccine clinical trials group, began
enrolling volunteers in its first trial.
In December 1992, NIAID launched its first Phase II HIV vaccine clinical trial.
This trial included uninfected volunteers with a history of high-risk behavior-injection
drug use, multiple sex partners, or sexually transmitted infections. Participants
were counseled repeatedly to avoid any behaviors that put them at risk of HIV infection.
Created in May 2000, the NIAID-funded HIV Vaccine Trials Network (HVTN) is a network
of clinical sites in the United States and abroad dedicated to developing a preventive
HIV vaccine by testing and evaluating candidate vaccines in all phases of clinical
trials. The network includes more than 25 sites in the United States, Africa, Asia,
South America, and the Caribbean.
HVTN's global capacity allows for rapid expansion as more vaccine candidates enter
the pipeline for testing and development, and for carrying out large-scale studies
of suitable vaccines. HVTN built upon the many accomplishments of the HIV Prevention
Trials Network and AVEG, two former NIAID networks that conducted preparedness and
HIV vaccine studies. Scientific creativity, along with collaboration among private
industry, academia, and government, are key aspects of HVTN's design.
In addition, NIAID's Dale and Betty Bumpers Vaccine Research Center (VRC) conducts
research that facilitates the development of effective vaccines for human disease,
with the primary focus of research being the development of vaccines for AIDS. Established
in 1997 by former President Bill Clinton as part of an initiative to develop an
AIDS vaccine and located in Bethesda, VRC develops and tests vaccine candidates
in all phases of clinical testing.
VRC works with scientists in academic, clinical, and industrial laboratories through
a program of national and international collaborations. The center actively seeks
industrial partners for the development, efficacy testing, and marketing of vaccines,
and focuses on developing new methodologies and training opportunities that
will benefit all HIV vaccine researchers.
Clinical Trials of Therapeutic AIDS Vaccines
Currently, there are no approved therapeutic vaccines for people infected with HIV.
To date, scientists have conducted more than 30 NIAID-funded therapeutic vaccine
clinical trials. Additionally, new vaccine candidates are being tested as both potential
therapeutic and preventive vaccines.
Therapeutic vaccine research started in the early 1990s with several trials in the
United States and Europe in volunteers on antiretroviral therapy (ART). In June
1992, AVEG began its first therapeutic vaccine trial, enrolling 55 HIV-infected
men and women. The experimental gp160 vaccine was found to be safe. The first therapeutic
vaccine trial enrolling asymptomatic HIV-infected children and HIV-infected pregnant
women began in 1993.
The current NIAID-funded network conducting therapeutic vaccine studies is the AIDS
Clinical Trials Group (ACTG). The group was created in 1987 as a network of domestic
clinical sites to develop therapeutic agents to treat HIV and opportunistic infections
and malignancies. By 1991, ACTG was divided to create the Adult ACTG (AACTG) and
the Pediatric ACTG (PACTG). As the largest network of its kind in the world, ACTG
carries out a broad scientific, therapeutic, and pathogenesis-based research agenda.
Progress in the basic sciences and clinical research is moving scientists closer
to identifying vaccine candidates suitable for large-scale HIV vaccine trials. Researchers
continue to design and test novel ways to present HIV proteins to the immune system,
as well as develop new antigen-adjuvant vaccine formulations. Although the challenges
are daunting, scientists remain hopeful that they can develop safe and effective
A growing number and variety of experimental vaccines are entering clinical tests
in primates and humans, and more trials are exploring whether changing immunization
schedules, increasing booster doses, or using a combination vaccine strategy can
stimulate stronger, more durable immune responses. Currently, about 30 NIAID-sponsored
preventive HIV vaccine clinical trials are underway or planned for various stages
of testing in the United States and internationally. More vaccines will be studied
in the next 2 years than in the last 5 years combined, and thousands of additional
healthy volunteers from all populations will be needed in the coming years.
Information published courtesy of NIAID
This article was last modified in: 06/18/2012