I had the honor of interviewing Dr. Igor Grant, the Chair of the Department of Psychiatry at the University of California, San Diego School of Medicine. Dr. Grant is involved in research on HIV/AIDS, drug and alcohol abuse, and chronic stress in the elderly; currently, his research is focused on the effects of HIV, methamphetamine abuse, and the effect of aging on the acceleration of injury on the central nervous system (CNS) . In this interview, Dr. Grant talks about what led him to pursue research in HIV/AIDS, potential treatments, and the biggest challenges he has faced while researching the effects of the disease on the nervous system.
Chinmayi Balusu (CB): What is your particular field and what led you to pick it?
Dr. Igor Grant (IG): By training, I am a neuropsychiatrist, which means I am a medical doctor who also received training in psychiatry and some training in neurology. My research interest has always been in how different diseases and also drugs of abuse may impact the brain and behavior. HIV, as you know, is a viral disease and it can affect the brain. My interest in HIV came from my more general interest in neuropsychiatry and brain-behavior relationships.
CB: What are the effects of HIV and AIDS on the brain?
IG: HIV is a virus. When it enters the body, it can also enter the brain because obviously the brain is fed by blood vessels, and blood that is contaminated by the virus can allow the virus to enter the brain. Also, the virus causes inflammation, which means that there are certain kinds of immune cells in the blood that actually carry the virus. Sometimes, these will also cross into the brain across the blood-brain barrier. The virus can get in just by diffusion through blood, and it can cause an inflammatory response in the brain. The injury can be either functional, meaning the brain is not happy and not working right, or actual damage that can be irreversible.
CB: What type of treatments are there right now for HIV and AIDS?
IG: This is a bit of a complicated question so let me answer it in parts. Let’s say that a person belongs to a group where they are at a high risk of becoming infected with HIV. You could actually give them a low dose of medicine that can prevent the person from becoming infected in the first place. Now, once a person does become infected, you want to treat very early because what you want to do is prevent the spread of the virus throughout the body, especially to the brain. Once a person has an established infection, then your job is to eradicate the virus; however, as of now, none of our drugs are able to do so completely. What they can do is suppress the virus so that you can’t find it in the blood using regular tests. But the virus can still be lurking around in different parts of the body, including the brain. Then, you have to be sure that you keep treating the person with whatever are the most effective antiviral drugs. Not everyone responds to these medicines in the same way. It depends on your own physiology as well as the characteristics of the virus. Viruses have a common ancestry but they have some differences. Some viruses are more sensitive to one drug compared to others, but as long as you can keep the virus under very good control, you are less likely to have the various effects of the disease. The final point is that there is some research that says some of these antiviral drugs are better at getting into the brain than others, so they may possibly be more effective. The blood-brain barrier is set up so that it doesn’t allow random things in there and so sometimes it does not allow medicines. You have to find the medicines that penetrate into the brain.
CB: What kinds of drugs are used to treat HIV?
IG: There are different classes of drugs, such as antiviral drugs. What antiviral drugs try to do, in general terms, is they try to interfere with different parts of the virus’s reproductive cycle. The way HIV works is it gets inside your cells, mostly the immune cells, and it hijacks the genetic material of that cell to make its own genetic parts. So what you want to do with these medicines is interfere with different parts of the cycle of replication of the virus. The current treatment involves giving several classes of drugs so that you kind of hit the virus at several points because biological organisms are built to get around problems. The virus can evolve and it can start to do different things to get around the drug. But if you have several points of blockage it’s much more difficult for the virus to develop resistance.
CB: When it comes to the virus getting across the blood-brain barrier, is there a certain way in which the spread of HIV would have a further impact on the brain?
IG: Inflammation is an important part of how the HIV disease progresses. What the inflammation does, that is, if you have a lot of inflammatory cells and molecules in your bloodstream, is that it can actually change the permeability of the blood-brain barrier. It sort of weakens and opens up the doorway so that various kinds of leakage develop across the blood-brain barrier. If you have other diseases or conditions that also produce inflammation, that can make this process worse. For example, I am currently looking a lot at methamphetamine use. In addition to producing high stimulation, it can also kick up the inflammatory system by itself, without HIV. When you put the two together then you have more inflammation that can make conditions worse. So these coexisting diseases and certain kinds of drugs of abuse can all make things a little bit worse
CB: What is one of the biggest challenges you have faced in researching HIV/AIDS?
IG: I think one of the big challenges in working in brain disease, in general, is that as opposed to other organs, the brain is really not accessible to biological inspection. Let's say you have some sort of problem with your liver. You can actually put in a needle and take a little piece out to look at it. But you can't put a needle in the brain and take a piece out to take a look at it. You have to use methods, such as brain imaging and neurocognitive testing, which is basically testing people's memory, attention, etc. So there are a number of approaches, but, in a sense, they are all indirect. Some of what we know about the effects of HIV comes from studies of people who have died from these diseases. We can look at their brain specimens and do autopsies. So that's one big challenge in this field: you can’t actually take the organ and look up pieces of it. A lot of it is inferential.
CB: Even though more than 50% of patients with HIV have been diagnosed or will be diagnosed with neurocognitive disorders, why do you think it is not very well-known?
IG: I think in part it’s because many of these cognitive disorders are very mild in nature so they’re subtle. You need to very carefully evaluate a person's memory, attention, and other functions to detect it. Often people with HIV will say: “You know I'm actually not as sharp as I used to be. I kind of lose track of things more than I used to.” It’s not the case where people are wildly demented, but there is a small subset of people who develop dementing disorders. In the past, before we had really good treatments for HIV, the rates of these more severe cognitive disorders was much higher, about 15 percent. A lot of those are what we call asymptomatic, meaning that unless you look for it or unless a person reports it you can’t find it.
CB: Is it possible that HIV can increase the risk of developing dementia, such as Alzheimer’s?
IG: We don't know that for sure. It’s more likely the case that people who have chronic HIV disease, even if it's well-treated, still have this inflammatory response that is in the background. What that can lead to is cardiovascular disease and cerebrovascular disease, so there’s some evidence
for these processes, as opposed to Alzheimer’s itself. Let me put it this way: our organs have a limited number of ways in which they respond to injury. If you take the liver, for example, and give it some kind of poisonous substance, the person will turn yellow because of jaundice. The brain is the same, whether it's developing a problem through an Alzheimer’s process, vascular injury, or because of tiny strokes and problems like that. It hasn't been determined for sure. We’ve looked at the brains of some people with HIV who died in their fifties or sixties, and they have some of the protein changes that we find with Alzheimer's and Parkinson's more than we would expect at that age, so it could be multiple factors coming together.
CB: What are the current stages doctors use when determining the severity of a patient’s condition?
IG: First of all, there could be no complications, so the person is just normal. As you said, 50 percent or more have no problems at all. If you look at their brains after they die, their brains look fine. The first stage is what we call asymptomatic neurocognitive impairment (ANI). I consider the ANI stage as kind of a preclinical stage. There’s something there but the patient is basically doing okay. The next stage is mild neurocognitive disorder which means that the person has some impairment in memory, attention, or whatever it may be, and it has some effect on their daily life. For example, if they are students it takes them a lot longer to study something or to comprehend something. They need to exert a lot more effort. People may start relying on other people to help them or use a lot more technology. The final stage is the stage of HIV dementia where a person has cognitive dementia, and they are no longer able to function well.
CB: Does age play a role in how severely HIV/AIDS affect the brain and nervous system?
IG: Yes, it does to some degree. First of all, unfortunately, the older you get, the less good your cognitive function is in certain areas. There is kind of an unfortunate line that shows that if you’re 60 or 70 you’re just not doing as well on cognitive functions. Older people are usually fine with verbal skills so there is an age-related decline naturally even if you don’t have any disease. What we find with HIV is that the decline is amplified. It’s as though if you tested someone who is 50 or 60, they might be performing like a 55 or a 65-year-old.
CB: What is the connection between HIV/AIDS and syphilis?
IG: There is not a direct connection except that there are two things: they are transmitted similarly through unprotected sex with an infected person and syphilis can produce lesions or sores in the sexual organs. HIV can enter your body easier if there are these sores where the mucosal barrier has broken down. For example, we have a lot of germs in our mouth but our body is protected all the time by the mucosa, the moist skin inside of the mouth. If you have sores you’re more likely to get an infection of some sort. Syphilis itself can produce inflammation and a neurological condition. It does appear that people who are syphilis positive are more likely to have these neurocognitive impairments. It’s troubling because syphilis promotes this inflammatory state of HIV.
Chinmayi is a 17-year-old, undergraduate student at Columbia University who loves learning about the brain. She is the founder and CEO of Simply Neuroscience (IG: @simplyneuroscience), a nonprofit organization dedicated to fostering students' interdisciplinary interests in the brain. She has received many awards for her research work with biomedicine and neurodegenerative diseases was named a finalist in the Intel International Science and Engineering Fair (ISEF) 2019. Outside of neuroscience, Chinmayi enjoys creating documentaries, practicing taekwondo, mentoring students, writing poetry, and going for long walks. LinkedIn: https://www.linkedin.com/in/chinmayi-balusu/