First large-scale study of HIV vaccine starts in South Africa

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.

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