World's first new HIV vaccine efficacy study in seven years gathers pace
Volunteers step forward for trial in lead-up to World AIDS Day
Cape Town/Pretoria/Durban – The world’s first HIV vaccine efficacy study in seven years is now underway at several South African research centres and volunteers have been joining up as World AIDS Day approaches.
The study, called HVTN 702, will establish whether an experimental vaccine regimen safely prevents HIV infection among South African adults. It involves a new version of the only HIV vaccine candidate yet shown to provide some protection against the virus and aims to enrol 5 400 men and women. This makes it the largest and most advanced HIV vaccine clinical trial to take place in South Africa.
“HIV has taken a devastating toll in South Africa – and we are still seeing about 1 000 new infections every day – but we now begin a scientific exploration that could hold great promise for our country,” says Professor Glenda Gray, HVTN 702 protocol chair and president and CEO of the Medical Research Council of South Africa. “If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the epidemic.”
The experimental vaccine regimen being tested in HVTN 702 is based on the one investigated in the RV144 clinical trial in Thailand led by the US Military HIV Research Program and the Thai Ministry of Health. The Thai trial delivered landmark results in 2009 and the experimental vaccine regimen it tested was found to be 31.2 percent effective in preventing HIV infection over the 3.5-year follow-up period after vaccination.
In the HVTN 702 study, the design, schedule and components of the RV144 vaccine regimen have been modified in an attempt to increase the magnitude and duration of the protective immune responses elicited by the vaccine.
“This launch represents a significant HIV prevention milestone. In earlier studies, this vaccine regimen improved on many of the antibody responses to the types of HIV strains circulating in South Africa, providing us the scientific basis to conduct this pivotal trial. This study will provide important insights into vaccine development to help prevent new infections and end the epidemic,” says Dr Larry Corey, principal investigator at the HIV Vaccine Trials Network (HVTN) which is part of the Fred Hutchinson Cancer Research Centre in Seattle and is responsible, overall, for the conduct of HVTN 702.
This study is being conducted solely at 15 research centres in South Africa and its protocol co-chairs are all local researchers: Professor Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town, Dr Fatima Laher of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital, and Dr Mookho Malahleha of Setshaba Research Centre in Soshanguve.
The 5 400 study volunteers are being randomly assigned to receive either the investigational vaccine regimen or a placebo. All study participants will receive injections on five occasions over the course of one year.
Drs Glenda Gray & Larry Corey talking to a participant at the Setshaba Research Centre.
She will participate in the HVTN 702 vaccine efficacy trial.
The safety of HVTN 702 study participants will be closely monitored throughout the trial, and participants will be offered established methods for preventing HIV infection. The vaccines do not contain whole HIV and therefore do not pose any danger of HIV infection to study participants. Despite these precautions, some study participants will become infected with HIV in a similar manner to other members of the community. They will be referred to local medical providers for care and treatment and will be counselled on how to reduce their risk of transmitting the virus.
Funding the trial are the National Institute for Allergy and Infectious Diseases (NIAID), the Bill & Melinda Gates Foundation, and the South African Medical Research Council (MRC).
The journey to HVTN 702
HVTN 702 begins just months after interim results were reported for HVTN 100, a smaller clinical trial, which found that the new vaccine regimen was safe for the 252 study participants and induced comparable immune responses to those reported in RV144. The programme of clinical studies on this regimen in South Africa is known as Uhambo, which means a journey.
HVTN 100 and HVTN 702 are also part of a larger HIV vaccine research endeavour led by the Pox-Protein Public-Private Partnership, or P5, a diverse group of public and private organisations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to advance scientists’ understanding of the immune responses associated with preventing HIV infection. P5 members include the National Institute for Allergy and Infectious Diseases (NIAID), the Bill & Melinda Gates Foundation, the South African Medical Research Council (MRC), the HIV Vaccine Trials Network (HVTN), Sanofi Pasteur, GSK and the US Military HIV Research Program.
More about the experimental vaccine regimen
The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox vector-based vaccine called ALVAC-HIV and a two-component gp120 protein subunit vaccine with an adjuvant to enhance the body’s immune response to the protein subunit. Both ALVAC-HIV (supplied by Sanofi Pasteur) and the protein vaccine (supplied by GSK) have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. Additionally, the protein subunit vaccine in HVTN 702 is combined with MF59 (also supplied by GSK), a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen includes booster shots at the one-year mark in an effort to prolong the early protective effect observed in RV144.