A Q&A With Dr. Warner Green
EDGE presents a Q&A with Warner C. Greene, MD, PhD, director of virology and immunology research at the Gladstone Institutes in San Francisco.
Q: What are some of today's biggest challenges facing HIV research today and the quest to end AIDS?
A: First and foremost, we are challenged by lack of public knowledge. People don't understand that the epidemic continues to grow. They don't realize how important it is to stay safe and get tested. And they don't realize that this is fourth most serious epidemic we have ever faced that is threatening to become the third.
You see, as scientists, we are not satisfied with controlling HIV/AIDS. We want to stop the disease once and for all. So we are challenged by the facts that we don't yet have a vaccine against the virus, we don't have a cure, and we don't understand why those taking antiretroviral medications (ARVs) are succumbing prematurely to non-AIDS illnesses associated with aging. At Gladstone, where I direct virology and immunology research, we are focused on finding solutions to each and every one of these large challenges.
Q: We are hearing about things like "condom fatigue," and that infection rates among youngsters is going up, is this true? Why do you think?
A: In a cruel dose of irony, the very ARVs that have saved so many lives -- by blocking HIV from destroying the human immune system -- also seem to be undermining efforts to stop HIV/AIDS: I believe that the effectiveness of these lifesaving drugs may have lulled many people into the false impression that this global epidemic is over. Many don't realize that the epidemic continues to expand.
In spite of this, other statistics suggest that people have dropped their guard against the virus. Do you know that new infections among young gay and bisexual men in the United States increased 22 percent from 2007 to 2010 ? Think of it -- a full 22 percent increase in HIV infections here.
At the same time, people are not getting tested, and some who do get tested are not on ARVs. In 2009, for example, 59 percent of HIV-positive Americans aged 13 to 24 were unaware of the fact that they were infected . And in 2011, only a third of HIV-positive people in the States had been prescribed ARVs . That means two-thirds may have been spreading the disease to others.
Q: Some people think we've already kicked HIV/AIDS to the curb. After all, there are plenty of drugs to keep HIV in check so that it doesn't progress to AIDS. True or false?
A: ARVs really are wonder drugs. But there is this unfortunate phenomenon that I mentioned before that is very troubling: many people taking ARVs wind up, later, suffering prematurely from diseases that usually occur in aging populations, such as cardiovascular disease, dementia, and liver disease. A full 10-15 years before non-HIV-infected people, those with the virus are developing these aging-related diseases. So folks are surviving longer. But they can really take a hit on the quality-of-life scale when they are struck early by these debilitating diseases. Anyone who thinks ARVs are a perfect solution is mistaken. We don't understand precisely what is going wrong scientifically, but our best guess is that persistent inflammation is at the root of the problem.
Q: How do you feel about HIV/AIDS education -- everyone is pretty much up to speed, aren't they? How is research helping?
A: Here again, I think there are a lot of surprises out there. A study last year from the Washington Post and the Kaiser Family Foundation revealed that a third of Americans harbor at least one major misconception about HIV transmission. More than a quarter of people were unclear about whether or not they could catch HIV by sharing a drink with someone who has the virus. And about a quarter thought that we have a cure for AIDs already.
Q: We've heard a lot of chatter lately about an AIDS-free generation. What do you think? Can we get there?
A: I think it's a great aspiration and I applaud the notion. But so much needs to change before that can become possible. And everyone can play a role. We need to talk about it more to increase public knowledge -- if everyone had all the facts and understood the grave ramifications of getting infected, we'd be doing a better job of preventing transmission, understanding what activities are risky, when it's important to get tested and when it's the right time to start with ARVs.
The percent of Americans who name HIV/AIDS as the most urgent health problem facing the nation dropped to 10 percent in 2012, down from 68 percent in 1987. This so-called AIDS fatigue has led to a lack of awareness of disease trends, prevention methods, and a general disregard for the threat this virus continues to pose.
In absolute terms, we are still facing an expanding HIV/AIDS epidemic with a new and unexpected complication. In order to better understand, prevent, treat and cure HIV/AIDS, we need to better understand three essential processes: the link between the virus and inflammation; the type of immune response needed to prevent virus transmission; and HIV's ability to establish latent reservoirs resistant to drug treatment.
We need to face facts about the urgent need for renewed awareness and new solutions. And we must all do more to support research to develop new and better solutions for preventing, treating and ultimately curing HIV/AIDS. The HIV/AIDS epidemic is far from over, and if we continue to let down our guard or waver in our commitment to treatment and prevention in the developed world, the virus will inevitably strike and strike hard.
Q: If you could say one thing about the fight to end AIDS what would it be? Why are you so passionate about fighting HIV? How has your research helped to date?
A: More than two decades ago -- when I was an attending physician on the wards of San Francisco General Hospital -- every single one of my patients had AIDS. And there wasn’t a thing that we could do about it. Every one of my patients died.
So it was very moving for me to join Gladstone to lead the charge against this deadly disease as the director of virology and immunology research in 1991. At the time, we didn’t know the full dimensions of the epidemic.
I’m proud to say that we’ve made many contributions since that time to stem the tide of HIV/AIDS. Our studies of HIV have also uncovered fundamentals of human biology along the way because viruses are professional hijackers of cellular processes. So our research has contributed to the development of those life-saving ARVs by helping unravel the basic biology of how the virus works. It has also led to a better understanding of the dormant, or latent form of HIV hiding in the body. And we’ve shown that a single pill known as Truvada can help reduce HIV-transmission when given to uninfected individuals at high risk. The FDA recently approved this drug as the first prophylactic, or preventative, drug to curb the spread of HIV.
But there is no time to lose for the 34 million people currently infected with HIV/AIDS around the world -- and the millions more we expect to acquire this virus this year and the next and the next. We must also help those in the developing world. I spend a lot of time in working in Africa and have witnessed, first hand, the devastation this disease is causing there -- most of the 7 million HIV-positive people without access to ARVs live in sub-Saharan Africa and 70 percent of new infections occurs there. Tragically, more than two-thirds of the world’s children who should be on ARVs do not have access to the drugs. We have gone really far with our efforts to end HIV/AIDS. But we urgently need to do more, much more.
Q: Who is someone you admire in the fight for HIV today?
A: I really admire Jeff Sheehy, who has been very active as an advocate for HIV research in the community and within our university. If you don’t know him, he’s the communications director at the AIDS Research Institute at UCSF. Jeff is also a patient-advocate member of the Governing Board for the California Institute for Regenerative Medicine, CIRM’s Independent Citizens’ Oversight Committee. He has been very active in raising awareness of the virus, making sure the latest findings are disseminated, and ensuring that scientists like me are aware of what really matters to the affected community. He and his husband Bill are now raising a young daughter. Jeff is one of the people who inspires scientists like me to do better work -- and to find a cure.
Q: Tell me about your science, what are you working on that could help us in the fight against AIDS?
A: As with all the diseases we work on at Gladstone, we are taking a multi-pronged approach to stopping HIV/AIDS. So some of our scientists are focused on preventing HIV transmission with Truvada. Others are attacking HIV latency by working on new ways to fight the virus when it "hides" within cells. This could finally make it possible to cure HIV-infected patients.
One of our young investigators is building on the Nobel-prize-winning stem cell discoveries of Gladstone scientist Shinya Yamanaka to genetically engineer laboratory animals to have human immune systems. These so-called humanized mice will let us study why some HIV-positive people, known as elite controllers, naturally control the virus and do not develop AIDS -- all in the absence of medications. This knowledge could help us mimic these individuals’ protective response in a therapy that could keep others from developing AIDS.
And another young investigator is testing the use of therapeutic interfering particles, or TIPs, to outsmart the virus. With genetic engineering, he can eviscerate HIV’s damaging payload -- while retaining its viral characteristics of contagion and mutation. Now we’re investigating if TIPs may replicate more efficiently than HIV -- thereby preventing the virus from destroying the human immune system.
In my own laboratory, we are currently focused on preventing HIV from becoming AIDS by testing existing medications that could block the depletion of CD4 T immune cells. Just a few years ago, we discovered at Gladstone that this depletion -- a reaction the body mounts in response to HIV -- is the fundamental cause of AIDS. It’s a response that leads to pyroptosis -- a fiery form of cellular death that can cause chronic inflammation at a cellular level. We hope to stop this inflammation and the death of CD4 T cells thereby creating an affordable, life-saving solution for the millions without current access to ARVs. The drugs have already been in clinical trials, so a lot of the regulatory hurdles have already been addressed.
Also, if we can effectively control inflammation, this treatment could also lead to a new way to stop the premature onset of aging-related diseases. This problem is the lead concern among the HIV-infected in the developed world, so a solution could be really important for the community here at home. And we are also investigating if HIV-induced inflammation expands the body’s reservoir of latent HIV. If it does, controlling inflammation may be key to ridding the body of this dormant form of HIV and achieving a cure.
This is one of the most exciting research areas of my career. We are tapping into the fundamentals of HIV/AIDS.
Dr. Warner Greene’s work focuses on the molecular mechanisms underlying the pathogenic effects of HIV infection, with special emphasis on the function of the HIV nef, vif, and vpr gene products. He is the author of more than 350 scientific papers and has been recognized as one of the 100 Most Cited Scientists in the world. After serving as a Senior Investigator at the National Cancer Institute and a Professor of Medicine and Howard Hughes Investigator at Duke University Medical Center, Dr. Greene accepted his current position as the Founding Director of the Gladstone Institute of Virology and Immunology in 1991. He is a member of the Institute of Medicine of the National Academies and a fellow of the American Academy for the Advancement of Science. He also serves as Co-Director of the UCSF-GIVI Center for AIDS Research, and has served as a councilor and president of the Association of American Physicians.