World AIDS Day was first recognized on December 1, 1988, to catalyze a global movement aimed at preventing and treating this highly infectious disease. Yet, today, on the 30th World AIDS Day, a preventive HIV vaccine has yet to be delivered.
Hope and efforts remain strong. Administered proactively, a vaccine could have a huge impact in reducing the global burden of HIV infections. But advances in HIV vaccine development have been disappointingly slow due to the complicated and adaptive nature of the virus.
Here, Paul Turner, shares his perspective on where we are today, lessons learned along the way, and why we can’t give up.
What are some of the greatest challenges facing HIV vaccine researchers?
People have no natural immunity to HIV to use as building blocks for a vaccine, and the variability of HIV types and its ability to rapidly mutate have made it difficult for vaccine development efforts to advance. Researchers also have found that animal models don’t reliably predict vaccine efficacy in humans, adding further roadblocks to progress.
Consequently, the Food and Drug Administration (FDA) and other regulatory bodies have not approved any HIV vaccines, despite decades of research. Yet, there are plenty of reasons to be hopeful.
Earlier this year, The Lancet published results of a study of a mosaic HIV-1 vaccine, the Approach study, which showed the vaccine was able to trigger anti-HIV immune responses in healthy individuals. The vaccine model was designed using a machine learning algorithm that analyzed HIV data to select a “mosaic” of HIV sequences from multiple virus strains in order to generate immune responses that can cover a broad range of HIV subtypes. The vaccine was also found to induce comparable and robust immune responses in humans and rhesus monkeys, and it provided significant protection against repetitive heterologous Simian-human Immunodeficiency Viruses (SHIV) challenges in rhesus monkeys, suggesting it may offer a reliable animal model for future testing. A tetravalent version of this vaccine is currently being evaluated in a phase 2b proof-of-concept study, called Imbokodo.
That’s just one of 38 clinical trials ongoing or planned for an HIV vaccine, as of November 2018, some of which are focused on the use of broadly neutralizing anti-HIV antibodies (bNAbs). bNAbs are produced by some people already infected with HIV, and these antibodies can recognize a variety of HIV strains or subtypes and can attach themselves to the surface of the HIV virus to stop it from infecting healthy cells. bNAbs have been shown to prevent most HIV strains from infecting human cells in the laboratory, and one study showed success in immunizing calves against HIV. However, to date scientists haven’t been able to prompt the human immune system to produce bNAbs through immunization.
What are some lessons you’ve learned in your years of vaccine clinical trials that could be applied to HIV?
HIV vaccine trials are a completely different beast form other vaccine trials, such as influenza, dengue and norovirus. The model we use in those areas is well established. We have clear guidelines dictating how long those trials should be run, which comparators to use, and what are appropriate efficacy endpoints – most of those questions have been settled. That’s not the case for HIV vaccine research.
But, two things do stand out: HIV vaccine trials need to be much longer, and sometimes larger, than other vaccine trials. This makes recruitment and retention, adaptive trial designs and managing numbers – people and data – essential. Those are things we know well at IQVIA.
Recruitment & Retention
In almost any country, the idea of volunteering as a healthy participant for a vaccine trial is intimidating. It’s important to identify the right demographic – sometimes global in scale – and engage potential participants in a meaningful way, informing them about what it means to get involved and dispelling any myths about the vaccine. In partnership with community healthcare workers, we help make participants feel a part of the greater prevention effort.
Once enrolled, engaging participants in the full length of the trial is critical. This can be challenging when the trial is four or five years in length – which is not uncommon for HIV vaccine trials. At IQVIA, we have developed models to help reduce lost-to-follow-up and dropout rates in these long-term trials. We also have a lot of experience in countries across sub-Saharan Africa, and other areas with high incidences of HIV, where it’s important to work with community people to keep the trial successful.
Adaptive Trial Designs
There’s been a lot of work over the past couple of years on how to use adaptive trial designs in HIV vaccine research. One concrete example is enrolling people into an HIV vaccine trial who are using another prevention method, such as Pre-Exposure Prophylaxis (PrEP). It is often necessary to adjust enrollment numbers accordingly to assess vaccine efficacy. This helps us by engaging people already interested in new prevention methods and better reflects the potential impact of a vaccine in a real-world scenario. Interim data analysis is also key in adapting trials for a change in sample size, vaccine arms and futility assessments.
Managing participants and data at scale
Finally, HIV vaccine trials require thousands of volunteers – sometimes up to 10,000 participants. Managing that number of people, the infrastructure required to engage them, and the capacity to store and evaluate trial data with a high degree of efficiency and integrity is essential. Our Infectious Diseases Center of Excellence at IQVIA has experience and best practices in place to effectively and efficiently support clinics, investigators and teams with the vast number of patients and associated data in such trials.
You’ve worked on the treatment end, supporting patients with HIV, as well as in prevention research. Why continue the time-consuming and costly efforts to develop a vaccine?
IQVIA’s reason for being is ultimately the people, whether patients or healthy volunteers, who enroll in clinical trials. And we cannot forget where we came from and the history of HIV treatment and prevention. I was on the forefront of the early response to HIV treatment here in the United States. It was an uncertain, and for many, a scary time. Today, many people are able to live full lives with the HIV treatments available. But my hope is that we can reduce the impact of the disease all together through greater prevention, and a vaccine would be a huge step in that direction.
How will we get there? Passion and long-term commitments across the global community of funders, drug developers, clinical investigators and community health partners. I’m proud to be a part of a very passionate – and compassionate – Infectious Diseases and Vaccines group here at IQVIA, where we are applying our broad and deep experience to help our customers ask better questions and solve some of the biggest treatment and prevention challenges today for a healthier tomorrow.