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HIV researcher at MU discovers new mutation in virus

Friday, November 9, 2012 | 6:00 a.m. CST
Stefan Sarafianos is a professor and researcher at MU who has specialized in HIV, among other diseases. Together with a team at his MU lab, he recently discovered a mutation of the virus less resistant to treatment by certain drugs.

COLUMBIA – With a disease as cunning and aggressive as AIDS, researcher Stefan Sarafianos always has to worry about the next development.

HIV, which causes AIDS, constantly changes, which means the disease must be monitored by a doctor all the time. If the virus mutates, drugs administered to a patient might no longer be effective.

Understanding the mutations, how drug resistant they are and which drugs are most effective are all questions that need to be answered for optimal treatment.

"Even when you treat the disease, it's still there, hiding. How do you kill something that's hiding?" asked Sarafianos, 49, associate professor of molecular microbiology and immunology at MU, as well as joint associate professor of biochemistry.

Sarafianos has devoted his career primarily to HIV research and is leading a medical crusade to improve the lives of those affected. He and his team recently made a discovery that has the potential to treat some patients more effectively.

They found a mutation of HIV – 172K – that is less resistant to certain types of drugs. The information will go into the database doctors use to treat patients. 

This development represents one small piece of the HIV puzzle and could benefit the 3 percent of HIV-positive patients who have the mutation.

HIV has entered its fourth decade. The virus began to assert itself in the 1980s, sparking a new era for medical research. The first AIDS cases were reported in 1981, and the CDC established the term acquired immune deficiency syndrome one year later.

It is now the sixth-leading cause of death among those ages 25 to 44 in the United States; in 1995, it was ranked the No. 1 cause of death in that age group, according to an article in the A.D.A.M. medical encyclopedia.

A new era in AIDS research

In the last 30 years, medications and developments in AIDS research have transformed the disease into a manageable one.

"We are doing much better than the first days of HIV with patients waking up in the middle of the night to take horse pills, up to 16 pills a day," Sarafianos said.

Although AIDS still has no cure, a number of treatments have been developed to increase and improve the lives of patients.

Highly active antiretroviral therapy has been very effective over the past 12 years using combinations of antiretroviral drugs, according to A.D.A.M., an online health information source.

Side effects remain, though they are considerably less severe than decades ago. Lipodystrophy (fat redistribution), kidney problems and nerve problems can be common for those being treated with antiretroviral medication.

A man devoted

HIV and AIDS are still relatively new to the world.

Sarafianos first heard about the AIDS epidemic when he came to the United States from Greece in 1985 to earn his doctorate at Georgetown University.

"I wasn't cut out for medical school because I'm squeamish with blood, but I loved biomedical studies," he said. "I jumped right into HIV work."

When a lab opportunity came his way six years ago, his wife, Mary, and four children, all under the age of 17, packed up from New Jersey and headed to Columbia.

What awaited him was a position as the chief investigator of his own lab at MU's Bond Life Sciences Center. Sarafianos and his team investigate HIV, hepatitis B and C and SARS, among other pathogens.

"A lot of the studies we do in the lab can be applied to not only HIV but different viruses," said Karen Kirby, a post-doctoral fellow at MU working at Sarafianos' lab.

She mentioned a coronavirus that recently emerged in the Middle East. "It's in the same family as the SARS virus, so we hope that a lot of the groundwork we have done can be translated to this virus," she said.

AZT to 172K

For the most recent discovery, Sarafianos worked with his lab of over 20 people, as well as Japanese researchers. He has previously worked with Dr. Hiroaki Mitsuya, chief of experimental retrovirology at the National Cancer Institute in Maryland.

Mitsuya is a leader in HIV research. He was one of the creators of AZT, or azidothymidine, the first antiretroviral government-approved drug for the treatment of HIV. It was approved by the FDA in 1987 as the first government-approved treatment for HIV, prescribed under the names Retrovir and Retrovis, and in 1990 for treatment in the early stages of HIV.

"We developed first three antiviral drugs in the 1980s. I believed it would be feasible to elongate the life of HIV-1 infected people, and now these people are living longer than those with Type 1 diabetes," Mitsuya said.

He said because of the nature of the virus, it will be very difficult, perhaps impossible, to get rid of the gene altogether from living cells, but the current treatments have increased the duration and quality of life for patients.

"HIV is just so cunning to mutate itself every day, so it's very difficult to develop an effective vaccine, but we have great drug treatments," he said.

After resistance to AZT developed, Sarafianos said researchers were back to square one.

"There was so much hope, and it was a terrible disappointment when the resistance happened so so fast," he said. 

The next generation

According to AIDS.gov, over 1 million people in the U.S. live with HIV, and one in five are unaware of their infection.

Sarafianos said awareness is not as much the problem in the U.S. today but rather a sort of complacency.

"I think in this country there is a considerable amount of awareness. But what is bad is that younger people tend to take more chances lately throughout the community," he said.

"Since there are great drugs now, HIV doesn't have the popularity and ironic glamor it used to in past decades," said Cale Mitchell, executive director of Rain-Central Missouri, which provides resources for those affected by HIV and STDs in 37 Missouri counties.

According to the Centers for Disease Control and Prevention, 39% of HIV infections in the U.S. in 2009 were from young people aged 13 to 29. People aged 15 to 29 made up 21% of the U.S. population in 2010.

"In mid-Missouri, we are not the epicenter for the disease. We still have 400 people we deal with in case management, but that doesn't include the hundreds of others out there whose disease is still evolving and aren't seeking treatment," Mitchell said.

In Missouri, 18,404 people have been diagnosed with HIV since 1982. Of those, 61 percent are still living. 

Sarafianos hopes to keep awareness up and looks positively at future progress globally, possibly with a microbicide that could be applied by women looking to protect themselves in areas such as Africa.

This might be a lofty goal now, but Sarafianos said prevention needs much more progress considering the great amount of treatment options.

The approval of an at-home HIV test might be an effective tool for prevention and awareness.

Community support

Local organizations such as Trail to a Cure fundraise and hold events for HIV research, as well as assist those living with HIV and AIDS.

"I think any kind of HIV breakthroughs are met with both enthusiasm and caution because the idea is incredible, but we also don't want anyone to think this is a cure," said Kevin Clohessy, member of the board of directors of Trail to a Cure.

Trail to a Cure organizes local events such as an annual walk, ride and run on the Katy Trail every May. Clohessy said the events bring together many people that are invested in HIV research, as well as some who are avid marathon runners or riders.

Clohessy said his organization took cues from Rain-Central Missouri, and the members of the two organizations often support each other's events.

"These are people we are dealing with, not just dollars, and they need help navigating their way through this disease," Mitchell said.

Utility and housing assistance, as well as specialized care, are provided based on need through federal funding.

Some patients travel from Columbia to appointments, so help with transportation is available.

Still, Sarafianos expressed concern with insufficient funding for research.

"It is worrisome that, financially, some struggle with finding resources for this disease," he said. "I am fortunate to have a well-funded program."

A single drug goes through several rounds of research and clearance before clinical trials are conducted where costs are extremely high, he said.

"We have to treat with our best weapon, or else we're helping resistance. We are going to go after this disease with full force," Sarafianos said.

Here is a timeline of HIV and AIDS.

Supervising editor is Jeanne Abbott.



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