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 the vaccine.
“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 volunteers.”
“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.