AIDS Researchers Optimistic About New Medications
AIDS continues to be a devastating disease, but the prospects of fighting it have never looked better, researchers say.
Less-complicated drug regimens are improving patients’ adherence to treatment, and the array of medications available continues to reduce the death rate despite problems of drug resistance, scientists at the 10th Conference on Retroviruses and Opportunistic Infections said here last week. Several newer and potentially more effective drugs are in clinical trials, and another dozen or so prospects are poised to begin trials.
“This is an exciting, important year for therapy,” said Dr. John Mellors of the University of Pittsburgh. “The pipeline is fuller than it has been for a long time.”
“It’s quite remarkable,” added Dr. Kevin DeCock of the federal Centers for Disease Control and Prevention. “You have to wonder what the end of the story will be.”
There are now 16 drugs approved to treat human immunodeficiency virus -- many of them more powerful and longer-lasting than the earliest therapies.
As a consequence, many patients are able to take two or three pills once per day, or even one pill twice daily, Mellors said.
“That’s a fantastic development” that makes HIV therapy more like treating hypertension and other more common diseases, he said. Such ease of use also is improving adherence to drug regimens. A few years ago, only 50% to 60% of patients took all of their pills. “Now the proportion is up to 75% to 80%,” Mellors said. Those results are reflected in survival.
Dr. Amanda Mocroft of the Royal Free and University College Medical School in London and her colleagues studied 9,803 people diagnosed with HIV in Europe from 1994 -- before cocktails of AIDS drugs became available -- to 2002.
She reported at the retrovirus conference that the risk of HIV patients developing AIDS or of dying from it had fallen 80% by 1998. Since then, those risks have been reduced even further.
“Even though therapy is not perfect, it is working,” she said.
Dr. Scott Holmberg of the CDC said he has seen similar results in a group of 1,769 HIV-positive people studied over the same time period. He noted that the number of deaths from AIDS has continued to decline, but that the overall death rate in the group has remained relatively stable over the last few years, primarily because HIV-positive people are beginning to live long enough to die from causes unrelated to their infection.
The prospects for surviving with the virus in the future look even better, Mellors said, because of the “bumper crop” of new drug candidates. All 16 drugs approved for treating HIV infections target one of two viral enzymes, known as reverse transcriptase and protease. The drug candidates in the pipeline target not only those enzymes, but six other viral processes as well.
The most anticipated of the drugs nearing approval is Fuzeon, commonly called T-20 and developed by Hoffmann La Roche and Trimeris Inc. Fuzeon is the first member of a new family of drugs called fusion inhibitors. It is designed to prevent HIV from fusing with the membrane of target cells, the first step in viral entry.
Fuzeon is expected to be approved by the Food and Drug Administration next month. It is a peptide that must be administered by an injection twice daily, like insulin. The drug is expected to be expensive but has shown great promise in treating patients whose virus has grown resistant to other classes of drugs. The cost of the treatment is not known.
Some patients in trials, however, have shown a resistance to Fuzeon, and Trimeris has developed a follow-up drug, called T-1249, to combat the problem. Dr. Diego Miralles of Duke University reported that two-thirds of Fuzeon-resistant patients who received T-1249 for 10 days had at least a 90% drop in virus levels in their blood.
It will be a couple of years before T-1249 can make it through clinical trials, but the drug should become available as resistance to Fuzeon becomes more common.
Another new drug, called TMC114 and developed by Tibotec Inc. of Belgium, is designed to treat patients who have developed resistance to protease inhibitors now in use. Dr. Keikawus Arasteh of the Auguste-Viktoria-Klinikum in Berlin reported that a short-term administration of TMC114 reduced blood levels of the virus in all patients by at least 90% -- and in some patients by 99%.
In four of 10 patients treated, he said, blood levels of the virus were undetectable. “That is a really exciting viral drop-off,” Arasteh said.
Dr. Daniel Kuritzkes of Harvard Medical School reported last week on preliminary results with a synthetic antibody called TNX-355 that covers the surface of HIV’s target cells, preventing the virus from binding to the cells and entering.
A single injection of the antibody, produced by Tanox Inc. of Houston, reduced blood virus levels by more than 95% and kept them low for two to three weeks, Kuritzkes said.
Another drug is being developed by Panacos Pharmaceuticals of Gaithersburg, Md. It inhibits the maturation of HIV late in its replication through a process that is not understood. The inhibition results in the production of malformed viruses that are unable to infect other cells, said Carl Wild, chief science officer at Panacos.
The company hopes to begin clinical trials of the drug, called PA-457, this year.
