The Brain and HIV

The man is in his early 60s and his medical plate is full: an HIV diagnosis four years ago and well before that he began treatment for diabetes and coronary heart disease. For the most part, these conditions didn’t stop him from juggling the many things he loves to do: swimming, museums and dinner with his partner of 24 years, seeing his grown children and grandchildren, volunteering at a high-risk behavioral health group in his town, gardening, cooking – and oh, if he didn’t have enough to do, he went back to school for the fun of it. His schedule is filled with nine credits at a local college.

A year ago, he began noticing something odd in his daily routines: he was finding it harder to cook. He was missing appointments. He’d read a book and forget most of it by the time he got to the closing page. He couldn’t find the right word for objects he’s known for a lifetime. Once he could speak four languages and now the only words in his head were in his native tongue: English. His attention span was shot.

“I can’t remember stuff,” is all he could say about this new problem.

He is now at the Memory and Aging Center’s HIV and aging research program because he wants to know whether his cognitive deficits are part of getting old or if somehow the virus that remains undetected in his blood is doing something to his brain. Or maybe it’s Alzheimer’s or bits of it all. He has come to the right place. For the last decade, researchers, clinicians, radiologists, psychologists and nurses have been asking that same question. More than 200 HIV-infected people over 60 have gone through testing and the findings point to a worrisome trend: there is growing evidence that the virus leaves its mark in the brain and that it could put people at risk for a host of cognitive and psychiatric problems.

The research, led by geriatrician Victor Valcour, MD, PhD, has expanded to all corners of the world: Thailand, Cambodia, Kenya, Tanzania, Nigeria and Uganda. Their work has led to the use of antivirals in the earliest stages of disease. Now, because of their work with partners in the International NeuroHIV Cure Consortium that they established in these countries, it is sometimes considered unethical not to treat HIV right away, especially in the days following exposure. The hope of their ongoing research is to understand the impact of the virus on the human brain at a time in history when the disease is, for the most part, well treated with a mix of medicines that keep the virus at bay in the body.

The brain, it seems, may be another story.

It is amazing (to me) that so few scientists study HIV and the brain. The Valcour lab is cranking out its fair share of scientific papers and their work is showing that the virus triggers an immediate inflammatory reaction in the brain even during the earliest stages of infection. Right away, there is evidence on neurocognitive tests that something is happening in the brain. About a quarter of people tested right before they begin antiviral therapy score two standard deviations lower than those who have not been infected with HIV. They also see the persistent signature of that inflammation over the years – even with the best of treatment.

“We think it sets the stage for later cognitive problems,” said Dr. Valcour. “We really need to figure this out.”

There are now likely 5,000 people over 60 in San Francisco living with HIV; hundreds of thousands worldwide. Dr. Valcour and his team want to change the trajectory for a brain under the influence of this virus.

Science is a funny business. Sometimes, the stage is set from youth. A kid has an idea to become a doctor and she grows into that. For others, who they grow into has very little to do with where they came from. Or maybe it does.

Back in 1960, Andre “Andy” Valcour asked Marthe Menard took their vows and four years later put down money on a dairy farm on Randolph Road in Morrisville, Vermont. They would go on to have seven children, two of whom were boys expected to take over raising cows and milking them full-time when they grew up. Poor Andy never got his wish. Andy barely made it out of elementary school and learned to work the land (his parents were also farmers) and Marthe had trained as a nurse. But no matter that the Valcour kids knew the hard work of farming they would all go off to earn their medical degrees, doctoral degrees, business degrees and public health degrees.

In college, Victor, who was born in the middle of his siblings, fell in love with an ambulance and literally spent ten years as an EMT. He was applying to medical school around the same time that a call came through that the chairman of the biochemistry department was coding. The team got to the lab and Victor ran into the scientist’s office. Someone was already administering CPR and Victor made his way to the guy’s chest and put the defibrillator in place. The screen at the end of the defibrillator line spit out a rhythm. “The guy’s in v-fib,” his colleague shouted. Zap. Zap. They were now moving the lifeless body out of the lab and to a hospital. Zap. His pulse returned.

Victor looked up and he’d saved the guy’s life in front of the dean’s office. Soon after, he applied to medical school there and got accepted. He would go on to obtain a medical degree in his home state medical school and later a doctoral degree from the University of Amsterdam. His medical school professors had hopes that the ambitious young man would become a rural doctor in Vermont.

But by his fourth year in medical school, Victor was doing clinical rotations around the world. For years, he thought he wanted to become an anesthesiologist. But his career path changed during an interview for an internship when a primary care doctor looked at him and said his mind: You would hate being an anesthesiologist. It’s not you.

And that was that. “In my entire life,” he now says, “nothing was ever planned.”

Four years later, another twist of fate would throw anesthesia off his resume. He would do an internship in internal medicine at Saint Joseph Hospital in Denver. He decided on geriatric medicine. He was interested in Alzheimer’s. Even as a farm kid he enjoyed the company of his elder neighbors. In medical school, he’d go home at night and rehash the best moments of his long day and there would almost always be the older face of a person with a long and interesting life story.

He was always drawn to the stories. He was not interested in diagnosing diseases as much as improving quality of life for older people. A colleague had seen an ad for a geriatric medicine fellowship in Hawaii – and he and his partner decided to follow their hearts to a tropical paradise. The couple packed their lives into a Penske truck and headed west. He would work at a Japanese hospital on the island of Ohau. He was also moonlighting at night. Soon after, a colleague asked whether he’d be interested in writing a grant around an HIV project. No, he said, I am interested in Alzheimer’s. “Well, you’ll never find a better way to start your career,” the guy shot back. “And, the university needs the grant.”

By 2000, the number of people with HIV in Hawaii was on the rise. Two decades earlier, people who thought their time was limited headed for the islands, and now with life-saving medicines they were growing old and tan in the Hawaiian sun. Dr. Valcour had an idea. He’d write a grant on HIV and the aging brain. The grant was submitted. He got a million dollars for the project. That grant led to other federal grants and he was well on his way with his research. With all the attention to the brain, he thought that he should do a residency in neurology. He had three schools on his list: two in California and one in Colorado.

He arrived at his interview at UCSF in 2005 and never left. Bruce Miller, the director of the MAC, said there was no reason to do another residency. Dr. Valcour signed on for a two-year fellowship and began doing neurological exams on people with all kinds of dementias. And he brought his research and his ideas with him. A friend from Hawaii, an immunologist by training, was heading to Bangkok with her husband, and she and Dr. Valcour started an HIV study there, with $70,000 in seed money that he had from one of his grants.

He started his own HIV neurocognitive research program at the MAC in 2007.

And that is why Joe, another research volunteer, has shown up today. He was in his 30s when he was infected with the virus that causes AIDS. It took a few years for insurance to cover the new medicines that changed the face of the epidemic. The antivirals worked to reduce his viral load. Today, he is 60 years old. Last year, he too began having cognitive problems. He forgets words and sometimes renames objects even though he knows what he is saying is wrong. He watches his new brain like a hawk. It plays tricks on him all the time.

Brain scans showed no hints of Alzheimer’s. Doctors diagnosed him with HIV-related neurocognitive problems.

Scientists from the Valcour lab will follow him over time to understand how the virus gets into the brain and alters cognition after decades spent on antiviral medicines. He will also have an opportunity to participate in an 8-week course on mindfulness training that could help reduce the stress of his new brain disease. Being here, he said, means that he’s on the cutting edge of science. “I’m in the right place to learn more about my brain,” he added.

In addition to his work on HIV and cognition, Dr. Valcour is also co-deputy director of GBHI.

 

Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaboration between UCSF and Trinity College in Dublin. She will be spending several months at UCSF writing about the inner workings of the brain and giving voice to patients and the doctors, nurses, psychologists, geneticists and researchers involved in building the foundation for a whole body of non-Alzheimer dementias that are often missed, lost or ignored.