|First Large-Scale HIV Vaccine Trial in South
A large-scale clinical trial of a candidate HIV vaccine — which
previously showed promise in smaller studies in the United States
and elsewhere — has now opened in South Africa. The study
plans to enroll up to 3,000 HIV-negative men and women, making
it the largest African HIV vaccine trial to date.
Conducted jointly by the South African AIDS Vaccine Initiative
(SAAVI) and the HIV Vaccine Trials Network (HVTN), the trial is
supported by the National Institute of Allergy and Infectious Diseases
(NIAID), part of the National Institutes of Health (NIH). The study
vaccine, provided by Merck & Co. Inc. (Whitehouse Station, NJ),
contains copies of only three HIV genes, not the entire virus,
so it is impossible for a trial volunteer to become infected from
“Our best hope of ending the AIDS epidemic is a safe and effective
vaccine,” says NIH Director Elias A. Zerhouni, M.D. “To achieve
that goal requires the concerted effort of governments, scientists
and private industry as well as participation by well-informed
“We applaud the South Africans for bringing this important trial
to fruition. This international partnership exemplifies the model
of collaboration needed to defeat HIV/AIDS,” says NIAID Director
Anthony S. Fauci, M.D.
In South Africa the trial is called Phambili (“moving
forward”). Also known as HVTN 503, it is a Phase IIb “test-of-concept” trial,
the first such vaccine study in South Africa. This type of trial
is designed to provide preliminary information on vaccine efficacy
and thus enable researchers to decide whether or not to conduct
a larger Phase III efficacy trial that could lead to licensure.
In smaller trials, the vaccine was found to be safe and to stimulate
cellular immune responses against HIV in more than half of volunteers.
To date, more than 1,800 people have received at least one injection.
Two years ago, the first Phase IIb trial of the vaccine opened
at sites in the United States, Canada, South America, Australia
and the Caribbean (see http://www3.niaid.nih.gov/news/newsreleases/2005/mercktrial.htm),
areas where a subtype of HIV called clade B predominates. That
trial is ongoing.
As in that study, the main objectives of HVTN 503 are to determine
whether the candidate vaccine can prevent HIV infection or, in
those who do become infected, lower the level of HIV early on.
Additionally, the new trial will determine if the vaccine, which
is based on clade B HIV, has the potential to protect against the
HIV clade C subtype prevalent in South Africa. Immune responses
in the first several hundred volunteers will be assessed to ensure
the vaccine induces promising immune responses in this population
against the clade C virus before proceeding to full enrollment.
Study volunteers must be healthy, sexually active, HIV-negative
men and women, ages 18 to 35 years old. Investigators will assign
them at random to receive either the test vaccine or an inactive
placebo injection. The trial is double-blind, meaning that neither
the researchers nor the volunteers know which a participant has
received. All volunteers will be regularly counseled about ways
to reduce their risk of acquiring HIV, and they will be given condoms.
Access to care and treatment for sexually transmitted infections
will be provided, and because recent findings indicate that medical
circumcision can reduce the risk of HIV transmission from women
to men, access to medical circumcision will also be provided to
male participants who desire it.
In South Africa, the trial is led by Glenda Gray, MBBCH, FCPaeds
(SA), of the Perinatal HIV Research Unit, University of the Witwatersrand,
based at the Chris Hani Baragwanath Hospital in Soweto. James Kublin,
M.D., M.P.H., of Fred Hutchinson Cancer Research Center, Seattle,
serves as study co-chair. The study is expected to recruit volunteers
at five sites in South Africa, located in Soweto, Cape Town, Klerksdorp,
Medunsa and Durban.
According to Dr. Gray, the study team has actively sought community
endorsement of and support for this clinical trial, both of which
are critical to its success. “Our communities here in South Africa
are faced with the burden of HIV on a daily basis, and the trial
investigators and study team have spent years developing a rapport
with the community so that together we can move forward in our
quest to identify improved approaches to prevent new HIV infections.”
The test vaccine contains a weakened adenovirus that serves as
a carrier for three clade B HIV genes. Adenoviruses are among the
main causes of upper respiratory tract ailments such as the common
cold. Because the vaccine contains only three HIV genes housed
in weakened adenoviruses, study participants cannot become infected
with HIV or get a respiratory infection from the vaccine. The study
aims to determine if the HIV genes will induce a cellular immune
response, producing immune cells that recognize and kill cells
infected with HIV.
The South African Medicines Control Council, the South African
Department of Agriculture and the U.S. Food and Drug Administration
have reviewed the trial and allowed the study to proceed. In order
to conduct the trial, sites also are required to obtain institutional
ethics and biosafety committee approvals.
NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.