Trizivir

Take one pill, twice daily. That's it.

This new regimen was approved by the Food and Drug Administration for Trizivir, the first anti-HIV medication to combine three drugs into one tablet. The three are all nucleoside inhibitors made by Glaxo Wellcome: zidovudine (Retrovir), lamivudine (Epivir), and abacavir (Ziagen).

Trizivir combines standard dosages of the three drugs. Its price equals that of the three drugs taken together, a Glaxo Wellcome representative said.

"Everything that we can do to make drugs easier for patients to take is a step forward," said Dr. Donald I. Abrams, assistant director of the Positive Health program at the University of California, San Francisco.

But Trizivir is composed of three nucleoside inhibitors, so it probably will not become a standard regimen. Standard highly active antiretroviral therapy combines two nucleoside inhibitors with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Current treatment guidelines from the Panel on Clinical Practices for Treatment of HIV Infection and the International AIDS Society do not recommend a three-nucleoside combination. "I don't think anyone's suggesting that taking three drugs from the same class is the best way to start things," Dr. Abrams said. But that could change. Both groups are evaluating the clinical trials data for Trizivir, said Dr. Paul Volberding, a member of both guideline panels. The guidelines are continually updated "living documents," available at www.ama-assn.org/special/hiv/ treatmnt/guide/guidtrt.htm.

Dr. John Bartlett, director of infectious diseases at Johns Hopkins University Baltimore, sees Trizivir as an attractive option for relatively healthy, treatment-naive patients who may have compliance difficulties and for patients on existing regimens who have adherence problems.

"Physicians who don't quite grasp the complexities of [HW treatment] might gravitate to this pill. It might help in practices where primary care physicians are forced to care for AIDS patients, such as rural practices," speculated Dr. Volberding, director of the Positive Health program at the University of California, San Francisco. "I would hope that this doesn't make people think HLV treatment is easy

Trizivir was as effective as standard highly active antiretroviral therapy in trials of treatment-naive patients with viral loads under 100,000 per mL of plasma. The data "indicate pretty dearly that a triple-'nuke' combo can be quite potent, and if it gives up anything in potency it can make up for it in adherence," Dr. Volberding said.

Dr. Donna Sweet of the University of Kansas, Wichita, is already prescribing Trizivir for patients who were taking the three nucleosides separately Abacavir hypersensitivity is the main concern with this regimen, she said. About 5% of patients develop hypersensitivity reactions, including fever, rash, fatigue, GI symptoms, and respiratory symptoms such as pharyngitis, dyspnea, and cough. In these patients, abacavir should be immediately discontinued and not restarted, because fatal reactions can occur within hours of rechallenge.

For patients new to the three-drug combination, Dr. Sweet advised initially prescribing Combivir (zidovudine plus lamivudine) and abacavir separately during the first month. If hypersensitivity occurs, abacavir can be withdrawn without altering the zidovudine and lamivudine schedules.

Once that concern is addressed, resistance still poses a potential problem. On first glance, taking three drugs of the same class doesn't seem advisable because any resistance would eliminate all three medications from future regimens.

Physicians eager to try Trizivir are hoping that strict adherence, much easier to achieve with a simple regimen, will minimize the development of resistance.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group