Pew Researcher Seeks to Crack Code on HIV Cure

When the HIV/AIDS epidemic gained momentum across the United States—and the world—in the early 1980s, the human immunodeficiency virus (HIV) was considered largely untreatable. Scientific strides over the past few decades have changed this outlook dramatically. Today, new methods of prevention, detection, and treatment have helped halt HIV transmission and made it possible for people living with the virus to carry on healthy lives.

But researchers who study HIV, such as 2020 Pew Latin American fellow Gustavo Vasen, know that much more work still needs to be done. Although modern-day treatments can keep the virus at bay, HIV is expert at surviving silently and undetected in our immune cells—making itself difficult to eradicate.

This interview with Dr. Vasen, who is among the team of scientists taking on this challenge at San Francisco-based Gladstone Institutes, has been edited for length and clarity.

HIV is currently considered manageable but uncurable. Why?

Courtesy of Gustavo Vasen, Ph.D.

HIV infects cells in our immune system. Most of the time, HIV acts like most viruses: It hijacks infected cells to produce new copies of itself, known as virions, that are then released to infect new cells. These infected cells either die soon after that (producing viruses can be quite toxic) or are cleared by our immune system. But sometimes, the virus infects a cell and becomes “silent,” meaning that the cells are infected but don’t produce the virus. This is called “proviral latency” —and it presents a problem.

Can you explain “proviral latency”?

Latently infected cells are like undercover viral agents because the immune system won’t kill them or clear them—even during treatment. Our current treatments block viral reproduction so that the viral particles produced by hijacked cells can no longer infect new cells. After a few weeks under treatment, the remaining virus-producing cells disappear and the patients become what we call “undetectable,” meaning there are no measurable viral particles in their blood. But there’s still a problem: The treatment can’t do anything against the latently infected cells. Because they don’t produce toxic viral particles, these latent cells survive.

So these latent cells can’t be eliminated by treatment?

Exactly. And the problem is that these silent cells can wake up and start producing viral particles again. This happens constantly; fortunately, the treatment is able to protect the patients from viral rebounds. But if for any reason the treatment is interrupted, the latently infected cells can re-establish the infection. And sadly, this can happen within a few weeks.

Where does your research fit in?

Researchers are focusing intensely on understanding the molecular mechanisms that lead to latent infections. They’re asking: Why does the HIV infection result in two fates, active or latent? And more importantly, how does the virus accomplish this? A great body of research shows that the host cell can actively silence the incoming virus. But experimental evidence also suggests that the virus itself has evolved to establish latency. My work focuses on the second hypothesis.

What have you found so far?

We’re digging into the molecular mechanisms that the virus uses to enter latency. And we’ve found that the amount of the viral protein known as “Tat” plays a major role in determining the fate of the viral infection.

Could this research help inform a cure for HIV?

Proviral latency is the main barrier for curing HIV: As long as we can’t eliminate or inactivate the latent reservoir of infected cells in patients living with HIV, we won’t be able to cure the patients. Understanding the biology of how latent cells start and persist is key to developing new avenues for treatment.

Are there any common misunderstandings about HIV research?

Research on HIV is a little bit a victim of its own success. Our current therapies are excellent and are becoming more and more tolerable. They’re being used not only to treat patients but also prophylactically or even given post-exposure to prevent new infections. This is all fantastic news and has led to the idea that we’ve solved the HIV problem. But in reality, we are far from it. HIV remains an unresolved pandemic, in which we face problems such as access to medication, adherence to treatment, tolerance to drug side effects, and the development of treatment resistance. We still very much need to find a cure.

You recently wrapped up your time as a Pew Latin American fellow. How did the program affect your work?

Pew has been an invaluable support in my career. Pew’s biomedical research community is fantastic: Not only have I met inspiring scientists, many of whom will become future collaborators, but also friends. On the other hand, I want to go back to Argentina soon to set up my own lab. Public funding in Argentina comes and goes depending on whether science is considered a government priority, but the startup grant that Pew offers for fellows to establish an independent lab in Latin America changes this equation. I’m very grateful, honored, and fortunate to be part of this supportive community.