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AIDS PROGRESS TO PLACE DEMAND ON BIG PHARMA?
30 Apr 2010
Regulatory Affairs
Significant strides are being made in the treatment of Aids thanks to scientists and pharmaceutical companies, with a number of breakthroughs emerging in recent months.
Researchers at Imperial College London and Harvard University have grown a crystal that reveals the structure of an enzyme called integrase which is found in retroviruses like HIV.
Antiretroviral drugs for HIV - of which there are currently more than 20 approved in the US and Europe including Epivir, Retrovir and Ziagen (GlaxoSmithKline), Zerit (Bristol Myers-Squibb) Viracept (Pfizer) and Prezista (Johnson and Johnson) - work by blocking integrase.
However, scientists did not understand exactly how these drugs worked or how to improve them prior to the discovery by the Imperial College London and Harvard University researchers.
The new study shows that retroviral integrase actually has quite a different structure to what scientists had predicted based on earlier research. As a result of this investigation, researchers can now begin to fully understand how existing drugs work and how they might be improved, as well as how to stop HIV developing a resistance to them.
As part of the research, the scientists also used Merck treatment Isentress and Elvitegravir - an integrase inhibitor being developed by Gilead Sciences - to observe how antiretroviral drugs bind to and inactivate integrase by soaking the crystals in solutions of the drugs.
Over the course of four years, researchers carried out over 40,000 trials and were able to grow just seven kinds of crystals, with just one of these being of sufficient quality to determine the three-dimensional structure of integrase.
"It is a truly amazing story," said Dr Peter Cherepanov, the lead author of the study from the Department of Medicine at Imperial College London.
"When we started out, we knew that the project was very difficult, and that many tricks had already been tried and given up by others long ago.
"Therefore, we went back to square one and started by looking for a better model of HIV integrase, which could be more amenable for crystallisation.
"Despite initially painstakingly slow progress and very many failed attempts, we did not give up and our effort was finally rewarded."
More recently, scientists funded by the Bill and Melinda Gates Foundation have found that herpes drug Aciclovir, which is sold under brand names like Zoviraz (Sanofi Aventis) and Zovir (GSK), reduced the risk of HIV-1 disease progression by sixteen percent.
And at the recent Conference on Retroviruses and Opportunistic Infections, there was further reason for optimism, as scientists suggested that currently available HIV drugs hold the key to future treatments of the virus.
Experts believe a cream, gel or vaginal ring that women and men could use as a chemical shield to protect themselves from sexual transmission of HIV would be a major step forward in preventing the spread of the disease, according to Reuters.
Dr John Moore of Weill Cornell Medical College told the conference: "The next wave of compounds is all going to be based on antiretroviral drugs."
Reuters reported that his team tested Pfizer's new drug maraviroc, or Selzentry, which is in a new class of drugs called CCR5 entry inhibitors designed to stop the HIV virus accessing human cells.
"The CCR5 inhibitors are compelling candidates as an alternative because these drugs are not being used for treatment in, for example, Africa," the news provider quoted Moore as saying.
Brian Williams, research fellow at the South African Centre for Epidemiological Modeling and Analysis, also recently highlighted the advances in antiviral treatments, but also stressed the need to use the treatments to stop the infection as well as save lives.
Speaking at the American Association for the Advancement of Science meeting in San Diego last month, he suggested that by introducing HIV screening programmes and following this up with immediate antiviral treatment for infected individuals, HIV infection could be contained within five years. This course of action could eradicate HIV/Aids within 40 years.
Kenneth H Meyer, professor of medicine and community health at Brown University, added: "The need to treat people with antivirals to improve their life and reduce their ability to infect others will clearly rise. The question is, can we keep up?"
