That’s why scientists have been in pursuit of therapies that can keep HIV under control without the need for lifelong therapy. According to a study just published in the journal Nature, researchers have discovered a promising approach that could potentially make that a reality.Just in time for World AIDS Day on December 1, we sat down for an exclusive interview with one of the study’s co-authors, Hanneke Schuitemaker, Vice President and Global Head of Viral Vaccine Discovery and Translational Medicine at Janssen Vaccines & Prevention B.V., to learn more about how the potential treatment could someday help millions of people living with HIV.
Q:
It’s been more than 30 years since the first case of AIDS was diagnosed, and we still don’t have a vaccine or a cure. Why is HIV so difficult to treat?
A:
Hanneke Schuitemaker: When you become infected, the HIV genome becomes part of your genetic material. HIV attacks the immune system, and it does something tricky: The virus hides in a dormant state in some cells, so the immune system can’t tell that the infected cells are there.
Antiretroviral therapy doesn’t actually cure patients because it doesn’t affect this reservoir of dormant, infected cells. In order to eradicate HIV from a person’s system entirely, we would need to “wake up” the cells containing the dormant virus, so the immune system can target them.
Q:
How were researchers able to achieve this in the lab during this study?
A:
The two-year study was done in non-human primates (NHPs) infected with simian immunodeficiency virus (SIV), which is very similar to HIV, and treated with antivirals. Researchers gave the NHPs a combination of a drug designed to draw the virus out of hiding, and a vaccine to bolster the immune system, so it could fight the infected cells.
One was a medication known as a TLR7 agonist, which caused the virus to start expressing its proteins on the surface of cells, allowing the immune system to “see” the infected cells again.At the same time, two components of a therapeutic vaccine regimen were administered to stimulate the NHPs’ immune systems, so that once the virus was unmasked, their immune systems could target it more effectively.
Q:
How promising were the results of the study?
A:
Very! Beyond our expectations. When the data came in, we were dancing on the tables.
All nine NHPs who received the investigational vaccine, in combination with the TLR7 agonist, showed a significant decrease in virus levels after we stopped the antiviral therapy. And in three of them, SIV was completely undetectable after an initial rise in viral load following antiviral therapy interruption.
Compared to NHPs who didn’t receive the treatment, the treated group’s viral load was 100-fold lower. Neither the vaccine alone, nor the agonist alone, produced those kind of results.
Q:
You’ve described this therapy as a “functional cure.” What does that mean?
A:
HIV can hide in the brain, so you can never be completely sure you’ve achieved total eradication, but a functional cure is the next best thing. What that means is that it could be a potential strategy for people living with HIV to stay undetectable long-term without the need for lifelong ART.
We’ve heard for years that a cure is impossible. The virus is just so good at outwitting our best defenses. So to get results like these really gives us hope for the future.
Q:
What’s the next step?
A:
The vaccine was well-tolerated—the agonist caused a fever because it triggers the dormant virus to become active—but there were no serious or worrisome side effects that would prevent the research from moving forward.
So we’re going to start looking at the combination in humans.
We have a clinical trial in Thailand where we only test the vaccine regimen. In this study, HIV-infected participants who are on ART will remain so until we can see the effect the treatment has on reducing the size of their viral reservoir. That may take two years.
Since these individuals started their ART very early on, the size of their reservoir is very small, so it may be difficult to measure a reduction in size. But the goal is to see if our vaccine can elicit the desired immune response.
Q:
If this approach produces promising results in humans, what could it mean for those infected with HIV?
A:
For one thing, it has the potential to reduce transmission of the virus and help control the epidemic—just like we’ve seen with new treatments for hepatitis C.
On a personal level, there’s still a lot of stigma for those infected with HIV, so achieving a functional cure would potentially give sufferers the chance to put the disease behind them and better move on with their lives.
They wouldn’t have to take medication every day for the rest of their lives, which would be a significant benefit, especially if someone is potentially going to be on treatment for 30 or more years.
Q:
As someone who’s long worked in this field, what did you think when you first saw the results?
A:
I’ve been in HIV research since 1989, first in academia and then in the pharmaceutical branch. We’ve heard for years that a cure is impossible. The virus is just so good at outwitting our best defenses. So to get results like these really gives us hope for the future.
