In collaboration with researchers around the world, Stefan Sarafianos, associate professor of molecular microbiology and immunology at MU, and his team have made discoveries in HIV research that could lead to more effective treatment.
Working with researchers in Japan, the National Institutes of Health and the University of Pittsburgh, they found a mutation of HIV called 172K that can affect the virus's drug resistance. This information can help doctors better individualize therapies for patients, Sarafianos said.
"It's part of a puzzle," Sarafianos said. "The more information like that you get, the better you can design regiments that are more suitable, more efficient. That’s part of our larger studies of trying to understand drug resistance and drug susceptibility of various viruses. This is just the latest of the things that we've been doing."
HIV is constantly mutating, and there are multiple variations of the virus, Sarafianos said. Identifying the type of virus helps doctors figure out which treatment will be most effective for a particular patient.
"Before you start a patient on a certain therapy, you first check what kind of flavor the virus is because not all HIV viruses are the same," Sarafianos said. "So, you want to have a good picture of what exactly the sequence is. When you identify certain mutations that make the virus more or less susceptible to certain drugs, then you can predict what would be the best therapy for that patient."
The discovery of 172K provided two major findings, postdoctoral fellow Lefteris Michailidis said.
"First is that is that you can have a polymorphism, and this can affect your resistance to other drugs," Michailidis said. "Another is that this can affect not only one class of drugs but two different classes of drugs. There are two major classes: nucleoside analogs and drugs that are not NRTIs (nucleoside reverse transcriptase inhibitors). What we show in this paper is that this specific polymorphism can affect resistance to both classes of drugs."
Sarafianos and his team are continuing to work with EFdA, a new treatment for HIV they developed. EFdA targets the HIV enzyme responsible for viral replication. It has a unique chemical structure that is not found in other NRTIs, Michailidis said. EFdA is up to 60,000 times more potent than existing HIV treatments.
"It works with a different mechanism," Michailidis said. "The structure of the drug is so different than the drugs of this class, the previous drugs lack a component. That is very important, the component that this has makes it so potent."
Sarafianos and his team published that EFdA works well in large animal models. Health care company Merck & Co. Inc. entered into a licensing agreement with pharmaceutical company Yamasa Corporation to develop EFdA.
"Now, Merck picked it up, and hopefully it will go into clinical trials, so we are very excited about that," Sarafianos said. "What we're interested in now is what would be the best combination for patients. No drug is good by itself. So we are trying to find the most efficient combinations in terms of resistance and in terms of potency."
The effectiveness of HIV treatment has made significant progress throughout the years, Sarafianos said.
"I think we have a very good panel of drugs that can treat HIV, to the point where it's better to get diagnosed with HIV than (Type 1) diabetes, so to speak," Sarafianos said. "The life expectancy for someone who has (Type 1) diabetes is worse than someone who has just been diagnosed with HIV."
Many of these drugs come with side effects, but eventually the virus develops a resistance to all of them, Sarafianos said. Researchers have to keep developing new drugs, trying to develop a drug that is easy to take and has the least amount of side effects.
"We want these drugs to be something the patient can take in the long term," Sarafianos said. "These are not like antibiotics where you take it for a week. You need to be able to take it for the rest of your life. Even the smallest side effect, it's cumulative. So we want to understand the long-term effects of these drugs and come up with the least possible side effects."
Though there are more than 30 drugs to treat HIV, there is no drug to prevent the virus, Sarafianos said.