'Never give up': Researchers' tireless quest for HIV vaccines leads to Cape Town

Fred Hutch is known for its innovative work in fighting cancer but for almost 15 years, the center has also been key in a global effort to find a vaccine to halt another devastating disease – AIDS.

The Hutch runs the HIV Vaccine Trials Network (HVTN), the world’s largest consortium of researchers and educators working together to develop a safe and effective vaccine against HIV.

The network was launched by Hutch President and Director Dr. Larry Corey in 1999, a few years after the organization expanded its mission to include infectious disease, and has since grown to encompass 27 cities on four continents: North America, South America, Europe and Africa.

This week, the Hutch is opening a state-of-the art vaccine lab in Cape Town as it gears up to launch HIV vaccine trials there. The lab will analyze trial participants’ blood samples and study how their immune systems interact with the vaccine and with the virus.

The opening of the lab coincides with a conference co-hosted by the HVTN and the South African Medical Research Council. It marks the HVTN’s first meeting outside of the United States. The network is partnering with the South African government as it moves forward on its efforts to expand HIV vaccine research in the region.

“With partners and principal investigators around the world, we are moving the field forward to find the vaccine we need to stop the HIV/AIDS pandemic,” said Jim Maynard, the HVTN’s associate director of communications and community engagement.

The HVTN team is driven by the urgency of finding an end to HIV. Since the start of the pandemic, an estimated 36 million people around the globe have died of AIDS-related illnesses, according to UNAIDS. In 2012, there were 35.3 million people living with HIV.

A network around the world

The initial grant of roughly $700,000 Corey secured from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), funded the establishment of a core operations center at Fred Hutch, which is responsible for choosing the vaccines to be tested, designing clinical trials and protocols, processing trial samples and interpreting results.

The network, which is primarily funded by NIAID, works with researchers in various countries to run trials. While the dozen NIAID-funded sites across the U.S. are associated with universities, hospitals, and health organizations, some of the smaller sites lack the same infrastructure. In Iquitos, a city in the Peruvian rainforest reachable only by boat or plane, the HVTN clinic is run by two independent researchers.

While the network now attracts some of the brightest minds working in the field, it has had its share of challenges. The HVTN was controversial in the early days even within the Hutch, Chief Operating Officer Banks Warden said.

“Anything that wasn’t cancer, people wondered why the Hutch was involved,” he said.

HIV can be tied to cancer -- an estimated 25 percent of cancers worldwide are linked to infectious diseases. Those with HIV can be several thousand times more likely to develop various types of cancer, according to the National Cancer Institute, also part of the NIH.

The nature of a search for an HIV vaccine is inherently difficult and complex. HIV vaccine trials require large numbers of healthy participants willing to trust that they won’t be harmed – versus, for example, terminal cancer patients for whom a clinical trial may represent a last hope.

Determining how many participants are needed to find out whether a vaccine works is challenging, as is ensuring that participants accurately report behaviors that put themselves at risk of getting or transmitting HIV.

The work is further complicated by a lack of animal models that reflect how HIV progresses in humans, said Dr. James Kublin, the HVTN’s executive director.

“We don’t have the experimental models that reflect the dynamics of HIV infection without looking at thousands of people,” Kublin said. “This work is fraught with all sorts of challenges and difficulties.”

Committed to finding a vaccine

To date, the HVTN has conducted 48 HIV vaccine trials involving more than 8,200 participants. There have been only six large vaccine efficacy trials in HIV’s history, and only one has shown success. That trial, known as RV144, involved more than 16,000 volunteers in Thailand and was the biggest HIV vaccine trial to date.

Participants who got the vaccine had a modest -- 31 percent -- level of protection against becoming HIV-infected compared to those who did not receive the vaccine, according to results announced in 2009.

As expected in the difficult quest for a vaccine, there have been setbacks along the way.

In 2007, an HIV vaccine trial known as the Step study was halted after results showed that certain subgroups of U.S. participants who received the vaccine may have had an increased risk of HIV infection. As soon as the findings were known, a similar HVTN trial using the same investigational vaccine in South Africa, named the Phambili study, was also immediately stopped. Participants in the Phambili study continued to be monitored and results showed that the vaccine also caused an increased rate of infection among that group of volunteers.

Kublin said it’s unclear what caused the higher rates of infection, but the most plausible explanation is that the vaccine overactivated recipients’ immune systems, making them more vulnerable.

In May of this year, researchers stopped administering vaccines to participants in a U.S. trial after the NIAID Data and Safety Monitoring Committee concluded it would not reduce HIV infections by the target goal of 50 percent. Participants are still being followed, however, in hopes of learning more about the impact of the vaccine.

Developing effective vaccines is typically a long-term game, researchers say. The polio vaccine took almost half a century to develop, and the development of other vaccines has also stretched out for decades.

Given the complexity of HIV, which mutates at an astonishing rate and constantly evolves to resist treatment, finding a vaccine capable of outsmarting the virus is a formidable challenge.

But HVTN researchers keep at it in the belief that they will ultimately find an effective vaccine, Maynard said, and that reaching that goal is the only way forward.

“We know it’s the only thing that will ever truly stop the pandemic,” Maynard said. “These top researchers are people who have been fighting their entire careers. They never give up.”

Fred Hutch’s HIV Vaccine Trials Network opened a lab in Cape Town as we continue our quest to find a vaccine and end the march of AIDS. Follow our stories and photographs at www.Fredhutch.org/SouthAfrica.