WASHINGTON — Scientists today will present the first compelling proof that a new family of potent AIDS drugs can decrease or even prevent AIDS-related complications--and prolong life.
Researchers studying ritonavir, an experimental drug developed by Abbott Laboratories, will tell a major AIDS conference here that patients already very sick with AIDS who took the drug suffered far fewer symptoms of AIDS and lived significantly longer than those taking a placebo.
"It's very dramatic," said Andre Pernet, the company's vice president of pharmaceutical research and development, in describing the drug's impact on a group of patients with end-stage AIDS who had not responded to other treatments. "Patients tell us they feel better. They gain weight. They go back to work."
In the Abbott trial, the rate of episodes of AIDS-related illnesses fell by two-thirds among those taking ritonavir and the death rate was reduced by one-half, compared to a group receiving a placebo, company scientists told The Times on Wednesday.
"The big message here is hope," Pernet said. "We haven't had that before."
AIDS specialists have been very excited about the potential of this new class of drugs--known as protease inhibitors--and have been eagerly awaiting the first convincing evidence that they provide a clear clinical benefit to patients.
The findings will be presented at the Third Conference on Retroviruses and Opportunistic Infections.
Earlier this week, researchers studying another protease inhibitor reported that the compound, when used in combination with two standard AIDS drugs, suppressed reproduction of the virus to levels that were virtually undetectable in the bloodstream.
Until now, the most widely used AIDS drugs have been from a family known as nucleoside analogs, which are far less powerful. Both classes of drugs attack the virus at different stages in its reproductive cycle. The nucleoside analogs hit the replication process early on, while protease inhibitors target a critical later phase.
Experts do not yet know how well protease inhibitors will work over the long term, particularly in infected individuals who have not yet developed symptoms. One of the problems with all AIDS drugs is the eventual development of viral strains that are drug-resistant.
The results were seen more rapidly in patients in this trial because they already were extremely ill.
Nevertheless, "this is the first clinical data we've seen on these drugs--and it's terrific," said Dr. Robert T. Schooley, chairman of the scientific program committee for the conference. "We now have solid data that this class of drugs is beneficial to patients in terms of length and quality of life."
The randomized, double-blind, placebo-controlled study followed a total of 1,090 patients at 67 sites in the United States, Canada, Europe and Australia. All had advanced AIDS, with CD4 cell counts of less than 100 cells per cubic milliliter of blood.
CD4 cells are the primary target of the human immunodeficiency virus. Normal CD4 levels range between 800 and 1,000 cells; at counts below 100, the immune system is seriously compromised, leaving patients vulnerable to life-threatening infections and other conditions.
"We took patients who'd failed everything and were at the end of the line," said Dr. John Leonard, director of Abbott's antiviral research program, describing why the findings were so impressive. "Results could be seen fairly quickly" because, at that point, "bad things happen quickly," he said.
Thirteen percent of the 543 patients who received ritonavir died or experienced episodes of illness, compared with 27% of the 547 patients receiving a placebo. Disease progression was defined as the onset of a new AIDS-related illness.
Pernet said that episodes of illness dropped by two-thirds in the ritonavir patients.
"If you were getting sick three times a month, you might now be getting sick only once a month," he said.
The death rate among patients receiving ritonavir was 4.8%, approximately half the 8.4% mortality rate of those on the placebo.
In the study, patients took either 600 milligrams of ritonavir or placebo twice daily, and were allowed to continue taking nucleoside analogs if they already had been doing so.
About one-third of the patients in the study did not take nucleoside analogs, researchers said. There was no significant difference in outcome between those taking ritonavir alone and those who took it in addition to nucleoside analogs, they said. The majority of those on ritonavir alone also improved, just as those who took the combination, the scientists said.
Patients were followed for up to seven months.
The study was stopped after 5 1/2 months because the differences between the ritonavir group and the placebo group were so significant. Patients taking the placebo were given ritonavir.
The drug has not yet been approved for marketing by the Food and Drug Administration, although Abbott filed a licensing application on Dec. 21. An FDA advisory committee is scheduled to meet at the end of February and is likely to recommend that the drug be approved. If so, FDA approval could be swift, in a matter of weeks.
In December, the company also established an expanded access program for ritonavir, making it available via lottery to 2,000 AIDS patients worldwide. The FDA allows this kind of availability to experimental drugs in case of certain serious, life-threatening conditions, such as AIDS or cancer.