New AIDS Drugs Still a Distant Glimmer
March 13, 2002
There have been no major breakthroughs in AIDS therapies since the development of protease inhibitors six years ago. And with current therapies bedeviled by serious side effects and growing viral resistance, hopes are fading for a major advance. This was very apparent at the Ninth Retrovirus Conference in Seattle last month.
"It's becoming more and more difficult to make a major breakthrough" in AIDS research, said Raymond Schinazi of Emory University in Atlanta. "All the easy stuff has already been done."
"We weren't expecting a great deal this year, and we didn't get it," said Dr. Harvey A. Elder of Loma Linda University Medical Center.
AIDS therapies have extended lives and slashed the AIDS death rate from about 40,000 a year to 15,000, but the number of new infections has held steady at about 40,000 per year. Almost 1 million Americans are living with an HIV infection, according to new figures from the CDC.
As people live longer, new complications emerge and become apparent. Paramount among them are side effects caused by the drugs themselves, ranging from simple nausea and lethargy to abnormal fat distribution, high cholesterol levels, diabetes and, perhaps, an increased risk of heart attacks.
Given the complications, many are abandoning their drugs. New data show that those who quit are much more likely to develop AIDS or to die. It is hoped that brief interruptions, or structured treatment interruptions, will assist viral control by exposing HIV to the immune system. Several studies of this approach have yielded no new results. However, a new European study did look at the effect of total withdrawal. According to Dr. Jens D. Lundgren of the EuroSIDA Coordinating Office in Denmark, a 25-country study of AIDS treatment regimens found that 16 percent of the 3,610 patients studied have stopped taking their drugs due to side effects. Those who did stop were six times as likely to develop AIDS or to die as those who continued receiving the drugs. Those who stopped for a while and then resumed treatment were still twice as likely to die.
The constantly mutating HIV has continually frustrated researchers. Indeed, the whole point of combination therapy is to reduce viral replication sharply so that the virus cannot mutate. Many times the virus simply mutates despite the decrease in replication. Today, some patients carry viruses that are resistant to many or all of the 15 drugs used to treat HIV. "These are patients who really need new options desperately," said Dr. Martin Markowitz of the Aaron Diamond AIDS Research Center in New York.
Tipranavir is a new protease inhibitor that binds more tightly to the active site of enzymes, clogging the site and preventing the normal function of the virus. "It interacts in a more flexible manner with protease so it is able to bind to drug-resistant HIV," said Markowitz. Unlike existing protease inhibitors, he said, it is actually more effective against resistant viruses than against unmutated ones. Markowitz has reported on a 48-week trial in which tipranavir was combined with the protease inhibitor ritonavir in 41 patients. The combination reduced the virus in the blood to undetectable levels, and none of the patients developed resistance to the drug.
Dr. Brian Gazzard of Chelsea and Westminister Hospital in London described a new reverse transcriptase inhibitor called TMC125 which seems also to be effective against resistant viruses. He and his colleagues gave the new drug to 12 patients for a week. The drug slashed the virus replication by 99 percent even in patients who were resistant to other reverse transcriptase inhibitors. "That's a drop unlike anything we've seen before," said Dr. Joep Lange of the University of Amsterdam. "We need to understand why it has this particular potency."
The greatest long-term promise of new drugs, however, seems to lie in those that attack other parts of HIV's replication cycle, such as its entry into white blood cells. To enter these cells the virus must bind to two receptors, one called CD4 and one called CCR5. Researchers announced some progress on a drug called SCH C developed by Schering-Plough Co.
Finally, there is some good news for patients infected with HIV and the hepatitis C virus. Researchers led by Dr. Raymond Chung of Harvard Medical School, under a government-sponsored study, have been cautiously using the most powerful anti-hepatitis drug, interferon alpha 2-a, called Pegasys, with the conventional form of interferon. At least 90 percent of patients can tolerate the drugs and by 24 weeks, 44 percent of those receiving Pegasys had undetectable levels of hepatitis C virus in the blood.
Los Angeles Times
03.11.02; Thomas H. Maugh, II
This article was provided by U.S. Centers for Disease Control and Prevention. It is a part of the publication CDC HIV/Hepatitis/STD/TB Prevention News Update. Visit the CDC's website to find out more about their activities, publications and services.