Antiretroviral drugs developed by some of our nation’s leading scientists have been extraordinarily effective against HIV, the virus that causes AIDS.
These treatments have turned what once was a death sentence into a manageable, chronic condition. Thousands of people who likely would have died have instead gone on to live long, full, otherwise normal lives.
And yet, a cure for HIV has not been found.
Why is that?
Courtney Fletcher, Pharm.D., dean of the UNMC College of Pharmacy, is first author on a study published in a recent issue of Proceedings of the National Academy of Sciences that takes the first step toward answering that question.
The work of Dr. Fletcher and his collaborators’ was funded, in part, by a pair of National Institutes of Health grants.
“It’s not a huge breakthrough,” Dr. Fletcher said. “But we previously couldn’t have a rational discussion about why we couldn’t completely suppress replication of HIV throughout the body, which is a prerequisite to curing HIV infection. And now we can.”
Some would call that a huge breakthrough.
Turns out, while anti-HIV drugs are effective at fighting the virus, these drugs are less effective at getting to where the virus actually replicates – in lymph and gut tissues. The drugs let patients live with HIV, but the persistent low-level replication keeps the virus from ever being completely knocked out.
In short, Dr. Fletcher and his collaborators found that perhaps we haven’t been able to cure HIV because these drugs aren’t getting where they need to go in high enough dosages.
Dr. Fletcher compared it to the challenge faced by those working to get treatment through the blood-brain barrier.
Now, scientists who work toward a cure for HIV are clear about the challenge. To reach these findings, Dr. Fletcher collaborated with a team that included University of Minnesota colleagues Timothy Schacker, M.D., director of HIV Medicine, and Ashley Haase, M.D., Regents’ professor and head of microbiology.
“These are complex questions that require expertise from many disciplines to get data so we can understand what is going on,” Dr. Schacker said. “This is a great example of the team science we need to cure this disease.”
Dr. Fletcher used highly specialized and sensitive methods, developed in his laboratory, for measuring drug levels inside cells obtained from lymph nodes and gut tissues.
Drs. Schacker, Fletcher, Haase and their collaborators are working on a comprehensive study of all available anti-retroviral drugs and some new investigational drugs in an effort to identify a combination that will provide maximum penetration into lymph nodes and more effectively stop virus replication.
Dr. Fletcher has been working on HIV/AIDS drug research since the early 1980s. He was part of a team working on drugs for treatment of another viral infection when they became aware of a devastating new viral infection, HIV.
He was on the ground floor of HIV/AIDS research and the drugs developed for treatment.
When they started out, Dr. Fletcher and his colleagues contributed to AIDS patients being able to extend their lives by an average of six months. Now, years later, thanks to improved treatments, people with HIV can treat it like a chronic condition and live fairly normal lives.
A cure is not yet on the horizon.
“We will not cure this disease until we can completely suppress virus replication,” Dr. Schacker said.
But thanks in part to this latest work by Dr. Fletcher and his fellow investigators, we can now talk about that possibility.
When Dr. Fletcher came to the College of Pharmacy as dean in 2008 he assumed a full plate. But he did not put aside his research activities. He continues to be a force in HIV/AIDS research.
How unusual is it for a dean to be doing this kind of cutting-edge work?
Dr. Fletcher is one of two deans of Big Ten schools of pharmacy – Natalie Eddington, Ph.D., of the University of Maryland, is the other – to maintain active research labs.