Study to Have Global Impact on HIV Treatment

sph | June 10, 2015

iStock_000040450926SmallCROPPEDThe results from a new University of Minnesota-sponsored global HIV study show that when it comes to beginning drug treatments, the sooner patients start, the better—and the discovery could trigger a dramatic shift in how the disease is dealt with around the world.

Each year, roughly 2.1 million people contract HIV across the globe and an estimated 1.5 million people die from its AIDS-related illnesses.

The trial, called Strategic Timing of AntiRetroviral Treatment (START), began in 2009 and looked at what would happen if a group of HIV-positive—but otherwise healthy—people were put on antiretroviral drugs when their immune system’s CD4+ “t-cell” count was greater than 500. They were compared to a group who didn’t receive drugs until their t-cell counts dropped to 350. The 4,685 people in the study came from 35 countries around the world.

The results of the trial weren’t expected until 2016, seven years after the study began.

However, in a surprise development, accumulated evidence showed in late May that the results of the trial were already obvious:

Across the board—and in every country—early drug therapy helped bolster the health of HIV patients and it reduced their viral load, making them potentially less infectious to others as well.

Jim Neaton.
Jim Neaton

The study is being run by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). School of Public Health biostatistician Jim Neaton is the principal investigator for INSIGHT and shares more about the trial and its potential ramifications.

SPH: How were people selected to participate in the study?

Neaton: People were eligible for the study if they were infected with HIV, asymptomatic, and generally healthy—including having two CD4+ t-cell counts above 500. A cell count of 600-1200 is considered healthy.

They also had to be “treatment naive,” meaning they hadn’t taken antiretroviral medication yet. If they were women, they’d couldn’t be pregnant or breastfeeding, because in most of those cases they would have already been treated to avoid transmission to their babies.

Once the individuals consented to testing, they were randomized to begin therapy immediately or to wait until their CD4+ cell count declined to 350 or until they developed an AIDS event.

SPH: What made this the right time to do the trial?

Neaton: This type of global trial has been discussed for a long time. What made this an important study to do now were two things:

One, there was concern that the therapy itself increased the risk of what we call “non-AIDS diseases” like cardiovascular diseases, cancers, and renal diseases. We determined in a previous trial, called SMART, that interrupting therapy actually increased the risk of those diseases.

The other thing that made the trial important to consider doing was that shortly before the START trial began, another study showed that by taking therapy, you could reduce your risk of transmitting the virus to someone else.

From a public health point of view, it became clear that getting somebody on therapy was important for transmission prevention, but the overall risk-benefit to someone’s health was still uncertain. So that’s why we did the trial.

SPH: What were the main hurdles to performing the trial?

Neaton: This study was a challenge from the beginning.

For one, the University of Minnesota had to be the sponsor for the study because European trial regulations made it very difficult for the NIH to do so. The NIH basically told us that it would fund the trial, but the University had to sponsor it.

After several months of discussion with the University, the Board of Regents agreed to be the sponsor, to take on the liability of the trial.

In general, the disharmony in trial regulations around the world also makes what we’re doing very difficult. That said, I think we’ve learned how to do it the best it can be done within the various national health systems.

The effort is worth it because when you do a global trial and lots of sites and countries are involved, and the results are consistent across countries, it’s going to have worldwide impact. That’s important for a disease like HIV, which is far more prevalent in other parts of the world than in the U.S.

SPH: What sort of team effort did it take to complete this trial?

Neaton: This trial involved hundreds and hundreds of staff around the world and many people at the University of Minnesota.

I’m the principal investigator of the INSIGHT research group and part of the study leadership along with three co-chairs, Abdel Babiker in London, Jens Lundgren in Copenhagen, and Fred Gordin in Washington D.C.

The statistical and data management center and the operations core for the study are based at the School of Public Health. The four international coordinating centers in London, Copenhagen, DC, and Sydney help work with the sites around the world and really pay attention to detail on the day-to-day management of how studies like this should be run.

SPH: What do you want people to takeaway from the success of this trial?

Neaton: It’s important to do global trials with clinical outcomes to understand the risk-benefits of treatments. Too many studies are done using laboratory markers that don’t necessarily directly measure a person’s health. When you can do a trial on a global basis that concerns clinical disease and shows, in this case, that early treatment is beneficial, it can be much more convincing.

I tell the students that the world is becoming a much smaller place and global trials like this will be the norm in the next decade. Such studies are questioned because they’re expensive, and it involves sending funding to places outside the sponsoring country. But, people move around, diseases move around, and so there’s a real argument for doing global trials in many areas.

We’ve shown now that it’s possible to do them, and hopefully, they can have a big impact once they’re done.

~ Post by Charlie Plain



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