REVIVE: Large-scale HIV trial set to build capacity in clinical trial management in Africa

The introduction of anti-retroviral treatment (ART) for HIV infections in Africa has reduced the mortality rate from HIV by about 50% on the continent. Despite this incredible positive impact, HIV remains among the top five causes of mortality in Africa, with an estimated 460,000 deaths annually.

The Reducing Mortality in Adults with Advanced HIV Disease (REVIVE) trial, led by UCT and the Population Health Research Institute (PHRI) in Canada, and funded by the Gates Foundation, is a large, randomised controlled trial aimed at testing whether a cost-effective antibiotic intervention can increase survival in this group.

HIV, CD4 counts, and risk of infection

The presence of white blood cells that fight infection, known as CD4 cells, is a common way to measure the health of the immune system in people living with HIV, as HIV attacks and destroys CD4 cells. A low CD4 count renders a person unable to fight off basic infections. It has long been speculated that the high death rate of people with CD4 counts below 100 (a healthy CD4 count is over 500) is due to undetected bacterial infections that the body is unable to fight.

"In South Africa advanced HIV disease is a common problem.  Our patients are very vulnerable during this time when they have low CD4 counts and are starting or re-starting antiretroviral therapy. Deaths during these first few months of ART is a persistent problem which has been largely unchanged since the start of the ART era,” said Dr Charlotte Schutz, clinical research officer at UCT's Institute of Infectious Diseases and Molecular Medicine (IDM) and the South African national lead of the REVIVE trial.  
 

What makes the REVIVE trial significant is the size of it. With 8,000 participants across 14 African countries, we will be able to definitively answer the question of whether the provision of azithromycin can reduce mortality rates.

The REVIVE trial focuses on this vulnerable time period with the aim to reduce deaths by pre-emptively treating patients for serious bacterial infections with a broad-spectrum antibiotic called azithromycin.

“What makes the REVIVE trial significant is the size of it,” said Associate Professor Sean Wasserman at UCT's Division of Infectious Diseases and HIV Medicine in the Department of Medicine and scientific lead of REVIVE. 
 

“With 8,000 participants across 14 African countries we will be able to definitively answer the question of whether the provision of azithromycin can reduce mortality rates, potentially saving many thousands of lives over time.”

 

 

Building capacity in large-scale clinical trial management

A trial of this size is however a major logistical and administrative operation, traditionally the domain of global north institutions due to their resources and expertise. UCT’s partner institution, the PHRI has extensive experience in running large-scale trials, and are leading the coordination, contracting, and financial elements of the trial. The trial’s co-principal investigator, Professor John Eikelboom, is based at the Canadian McMaster University and PHRI and has provided critical leadership and support to the UCT team during this trial. Key to the partnership is the goal of building capacity in South Africa and Africa, growing a pool of individuals with the necessary experience to manage large-scale trials.

The REVIVE project team, and project manager, Elsa Gertenbach, are based within UCT’s Faculty of Health Sciences Clinical Research Centre (CRC) for the duration of the project. The project manager will also spend time in Canada as part of skills transfer from PHRI. Through this project there are plans to strengthen systems within UCT for clinical trials implementation.

“It is an enlightening experience to work between PHRI in Canada and the CRC in Cape Town,” said Gertenbach. “While the CRC has much experience in running industry and investigator-led trials, the scale of co-ordination executed by PHRI shows what can be done with expertise and the right investment in skills transfer and capacity building.”

Beyond UCT, there are other capacity-building activities across the 14 African countries involved.

“We have over 200 people working on the trial at different sites, all receiving training and gaining experience in clinical trial skills and practice. Along with this, we host monthly seminars and webinars across the REVIVE network,” says Associate Professor Wasserman.
 

 

Value of large-scale trials in Africa

Building clinical trial skills in Africa is critically important as many research questions on the continent go unanswered due to lack of skills and resources.

“The REVIVE trial gives us an opportunity to obtain other important information for this group of vulnerable people, particularly around HIV management across the continent,” said Wasserman. “This could potentially identify other ways to improve care of people with advanced HIV in sub-Saharan Africa.”

While UCT and other institutions in Africa are still a long way from having the financial and administrative resources to independently lead such large-scale trials, building human resources capacity on the ground is the first step.

“The REVIVE trial provides a huge opportunity for UCT to make a significant impact to a persistent problem of HIV management on the continent, how to protect this vulnerable pool of people presenting with advanced HIV and low CD4 counts,” said Professor Graeme Meintjes, Professor of Medicine at UCT and Chair of the Steering Committee for the REVIVE trial.

“And in the longer term the network and partnerships established through this trial, as well as experience and skills gained, will hopefully form the basis of further trials tackling questions most pertinent to the health of people in Africa.”

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