New HIV drug’s secret is flexibility

RUTGERS (US) — A new HIV drug’s effectiveness comes from its ability to adapt to the constantly mutating virus, changes that can prevent existing AIDS drugs from working.

The drug, called Edurant, is the first in three years to be approved by the Federal Drug Administration, a decade after it was first developed in 2001.

“For a drug to successfully make it to the finish line, countless obstacles must be overcome,” says Eddy Arnold, professor of chemistry and chemical biology at Rutgers. “As a researcher in biomedical sciences I can tell you that helping to create new medicines is something you always dream about.”

The innovative models developed by Arnold and colleagues explain not only why Edurant, and Intelence, approved in 2008, are particularly effective against drug-resistant viruses but can also be used in the development of treatments for a wide variety of other diseases.

Clinical trials for Edurant, which included more than 1,300 adults with HIV, indicated that 83 percent of those who were given this anti-AIDS drug for a 48-week period had undetected levels of HIV in their blood at the conclusion of the clinical trial.

The new drug can be prescribed as a once-a-day pill to HIV-positive adults who have not received any prior treatment or therapy.  Besides being available in the United States, a generic form of the drug will be made available to millions of people in Saharan Africa, India, and other developing nations.

“Development of this newest AIDS drug represents a wonderful example of the biomedical power that can be harnessed by scientific collaborations and partnerships between university, government, and private sector research enterprises,”says Kenneth J. Breslauer, dean of Life and Health Sciences at Rutgers.”No more satisfying and important outcome can result from university research.”

The scientific collaboration began in 1987 when Rutgers entered a partnership with Stephen Hughes, an AIDS researcher at the National Cancer Institute. Both were interested in understanding the molecular structure and function of reverse transcriptase, an essential part of the AIDS virus, not only for its fundamental significance, but also because they believed it would provide guidance for the design of more effective drugs.

Three years later, Arnold reached out to Paul Janssen, founder of Johnson & Johnson subsidiary Janssen Pharmaceutica, who had developed promising compounds to prevent reverse transcriptase from being able to create a genetic copy of the AIDS virus.

The Rutgers team suggested that crystal structures of the compound created by Janssen, bound to the reverse transcriptase enzyme, could help the company understand and improve its chemical structures and be used to develop more effective AIDS drugs.

They worked together for the next 13 years, during which time Janssen (who died in 2003) provided $2 million to help fund the Rutgers team’s research efforts to develop drugs that would be effective against drug-resistant mutants of the AIDS virus.

A pivotal breakthrough happened in 1998 when dapavirine—which works by preventing HIV from replicating its genetic material after the virus enters a healthy cell—was developed.

Further refinements of the drug led to the creation of  the newest anti-AIDS drugs whose clinical development was carried out by Tibotec: Intelence which has been on the market for three years, and Edurant, which was approved by the FDA in May and has shown exceptional potency against drug resistant HIV.

This year marks the 30th anniversary of the battle against HIV/AIDS.  According to the Centers for Disease Control and Prevention, more than 33 million people are living with HIV worldwide with 1 million residing in the United States.  Each year more than 56,000 become newly-infected with the virus.

“From the beginning, we knew this would be a long-term project, Arnold says.”Many challenges have been faced and overall it has been more like a marathon than anything else.”

Arnold’s research was funded in part by the National Institutes of Health.

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