8 February 2007
First large-scale study of HIV vaccine starts in South Africa
Phambili trial seeks 3000 participants
The South African AIDS Vaccine Initiative (SAAVI), which is supported by Eskom and the South African government, today announced the start of the first large-scale, test of concept HIV vaccine trial in South Africa. The Phambili trial, which will be conducted jointly with the international HIV Vaccine Trials Network (HVTN), also is the largest HIV vaccine trial in South Africa to date. Three thousand (3000) participants will be recruited from four provinces - Gauteng, North West, Western Cape and KwaZulu-Natal. The vaccine trial sites are located in Soweto, Cape Town, Klerksdorp, Medunsa and Durban. The trial name-Phambili-means going forward.
"This test vaccine is one of the most promising currently available internationally," says Professor Anthony MBewu, President of the Medical Research Council. "South Africa's conduct of this trial is a significant and exciting step forward in our search for a successful vaccine against HIV/AIDS. It is the first trial to gauge the preliminary effectiveness of a vaccine, and it's the largest to be conducted in South Africa. It will provide excellent experience for our researchers, clinicians and communities for future large-scale HIV vaccine trials."
The trial is known as a phase IIb or 'test of concept' trial because it enables researchers to test the concept that the study vaccine either prevents HIV infection or lowers HIV levels in those who become infected. While a phase IIb trial is not intended for licensure of a vaccine, the data from this study will guide future HIV vaccine development.
"South Africa is an excellent choice for this trial. Whilst there are numerous countries with similar high levels of infection, South Africa is unique in its good clinical infrastructure, a well-established national HIV vaccine initiative, and experience in running clinical trials. In addition, we have the necessary community involvement and education initiatives that are essential for running trials involving thousands of volunteers," says national principal investigator Professor Glenda Gray of the Perinatal HIV Research Unit at the University of the Witwatersrand. "South Africa is also one of a few African countries that have internationally recognized immunology laboratories capable of evaluating the immunogenicity of the vaccine within the country."
"This trial will answer several major scientific issues that face all of us in the field of HIV-vaccine development," said Lawrence Corey, M.D., principal investigator of the HVTN. "It will determine the usefulness of vaccines that induce high immune response to the parts of the virus that are similar between different strains of HIV-1."
Investigators for the South Africa vaccine trial will determine if this vaccine, which is based on clade B HIV, has the potential to protect against the clade C virus, the subtype prevalent in South Africa.
Additionally, the South African study is likely to provide important new data on how the test vaccine might work in a predominantly heterosexual HIV epidemic, how well the vaccine works in women, and whether the vaccine works in populations with pre-existing immunity to the viral vector used in the vaccine, according to Corey, who is also head of the Infectious Diseases Program and Virology Division at the University of Washington School of Medicine.
Volunteers will be healthy HIV-negative males and females, aged 18 to 35 years, who are sexually active and not pregnant.
SAAVI is committed to meaningful community involvement in HIV vaccine research and development. The Masikhulisane SAAVI Community Involvement Programme aims to educate communities to ensure informed decision making about clinical trials and also to provide support to Community Advisory Groups at the trial sites where the study will be conducted. Volunteers are encouraged to ask all relevant questions and to give truly free and informed consent.
A cornerstone of this vaccine trial is a commitment to the highest level of preventive care for all participants. To meet this commitment, all participants receive extensive, state-of-the-art risk-reduction counselling on a regular basis throughout the study, and high-quality male and female condoms are provided to participants. Participants are also provided access to care and treatment for any sexually transmitted infection during the study. Recent research studies have shown that men who are medically circumcised are less likely to become infected with HIV when they have sexual relations with women. As a result, access to circumcision will also be provided to male participants who desire circumcision.
The test vaccine to be used in this study was developed and manufactured by Merck & Co., Inc. and has already been extensively tested in the Americas, Africa and, Australia. Thousands of people have been involved in Phase I and II testing of the vaccine. The Phambili trial is conducted by the HIV Vaccine Trials Network (HVTN), which is funded through a cooperative agreement with the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health in the United States. The sites in South Africa are part of the HVTN's international network of HIV vaccine trial sites and are also clinical trial sites of SAAVI.
The test vaccine is known as the MRKAd5 HIV-1 trivalent vaccine. It is based on adenovirus - a common cold virus that has been modified so that it cannot cause a cold in humans or be passed from person to person. The adenovirus is the carrier (or vector) that transports copies of three HIV genes - called gag, pol and nef. The vaccine is made in the laboratory, and does not contain live HIV. The test vaccine therefore cannot cause infection.
The hope is that these HIV genes will induce a cellular immune response to HIV in the body producing killer cells that are programmed to recognise and kill cells that are infected with HIV. In previous trials this vaccine was found to be safe and to stimulate cellular immune responses against HIV in more than half of volunteers.
The trial design will compare the test vaccine to a placebo (a harmless substance). To eliminate bias, neither volunteers nor researchers know who receives the vaccine and who receives the placebo. The trial will last about four years. The trial has been approved by the South African Medicines Control Council, and the South African Department of Agriculture and successfully reviewed by the U.S. Food and Drug Administration. Approval has also been given or is pending by institutional ethics and bio-safety committees at all the different trial sites. In addition, there will be an independent Data and Safety Monitoring Board, a group of independent experts, not affiliated with Merck and Co. Inc, the HVTN, or the clinical trial investigators, who will carefully monitor the safety of the trial participants.
About SAAVI (www.saavi.org.za)
SAAVI is an initiative of the South African government, and a lead programme of the Medical Research Council. Founded in 1999 by Eskom, the Department of Health, and the Department of Science and Technology, SAAVI seeks to co-ordinate the research, development and testing of HIV vaccines in South Africa to arrive at an effective, safe, affordable and locally relevant AIDS vaccine as quickly as possible. SAAVI funds and co-ordinates activities of investigators at South African academic institutions. The activities include: laboratory development of vaccines; immunology; testing of vaccines in clinical trials; ethics and behavioural research; community education and mobilisation; and, actuarial science and bioinformatics. An emphasis has been on creating novel biotechnology platforms to develop and test HIV vaccines, and developing the clinical and social environment conducive to running HIV vaccine trials. SAAVI works and collaborates with key national and international partners, and has both an internal research and development arm aimed at investigating and developing novel candidate vaccines, as well as extensive and widespread clinical infrastructure for testing both our own and vaccines developed internationally.
About the HIV Vaccine Trials Network (www.hvtn.org)
The HVTN is an international collaboration of scientists and institutions whose goal is to accelerate the search for an HIV vaccine by sharing trial results and facilitating parallel, concurrent testing. The HVTN is a unique hybrid that combines the depth and diversity of the academic community and the flexibility of a commercial drug company. Working with industry and government, the HVTN seeks to expedite and co-ordinate the trial process, advancing vaccine candidates and building a body of knowledge around HIV vaccine trials. The HVTN is funded and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, an agency of the US Department of Health and Human Services (DHHS). The HVTN comprises more than 25 research institutions worldwide, co-ordinated from its headquarters at the Fred Hutchinson Cancer Research Center in Seattle.
About Merck (www.merck.com)
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories. Merck scientists have been conducting research to develop an HIV vaccine for nearly 20 years. The company also devotes extensive efforts to increase access to medicines through far-reaching programmes that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service.
About the National Institute of Allergy and Infectious Diseases (www3.niaid.nih.gov)
NIAID is a component of the United States 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.
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