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Drug sequencing for HIV

Data slim but growing on best approach

Drug sequencing for HIV

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Multiple possibilities

Which drugs work best

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(CNN) - Just a few years ago, potent "drug cocktail" combinations were hailed as a resounding breakthrough in the treatment of HIV and AIDS. But now -- at the same time that patients are living longer than ever before -- drug-resistant viruses threaten to take back hard won ground in the fight against the disease.

"Resistance is an increasing problem, not only in HIV but for all therapies for infectious agents," Dr. Richard Haubrich said Wednesday. "It's happened in the last 30 years with antibacterial therapies, and it's happening with HIV therapies."

Haubrich, an associate adjunct professor of medicine at the University of California in San Diego, spoke as part of a media conference on drug-sequencing strategies sponsored by pharmaceutical maker GlaxoSmithKline.

Today there are new "super pathogens" among bacteria and also HIV, continued Haubrich, one of several physicians and researchers participating in the conference. "But it doesn't mean that it is more virulent or causes more severe disease. It means that some therapies don't work as well as others."

The challenge for treating physicians is to discover the best combination of drugs and the proper sequence of those combinations to maximize survival and health for patients, said Dr. Benjamin Young, an attending physician with the Rose Medical Group in Denver, Colorado.

"The sequence is more complex for physicians," said Young, also a clinical instructor in medicine at the University of Colorado Health Sciences Center. "And the proper sequence is now essential in order to preserve therapy options for 10-20 years of treatment down the road."

Multiple possibilities

Some 18 antiretroviral agents now are available for prescription, either alone or in combination. Broadly speaking, the drugs fit three classes: protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors. Using these drugs, physicians have been able to suppress the AIDS virus to near undetectable levels in many patients. Still, drug-resistant forms of HIV are rebounding.

"We've known for a long time that HIV is a virus that mutates a lot," said Haubrich. "Look in one patient, and you find not just one viral strain, but hundreds, if not thousands. Any particular virus may have differences in its genetic code."

For some drugs, "resistance can occur quickly," he said. "In an increasing number of patients, therapy does eventually break through."

Young said studies indicate that for most patients, any particular drug or drug combination retains effectiveness for about 18 months before it becomes either less able to fight the virus or too toxic to continue.

"Over the last decade, we've learned that if the drugs are used in combination to suppress viral replication" the result can be improved quality of life, the Colorado physician added. Still, treatments must be individualized for maximum effectiveness.

"As much as we would like to have a cookbook approach, there are a lot of factors that go into the decision" of what drug combinations to try and what order in which to arrange them, said Haubrich. "We can speculate, and it becomes more of a personal opinion."

The results of small-scale studies on several drug regimens will be presented next week at a conference on retroviruses in Chicago, Illinois. The meeting is being sponsored by the Foundation for Retrovirology and Human Health in collaboration with the National Institutes of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention.

Which drugs work best

Deciding which drug or drugs to use depends most on "the one the patient is most likely to take and be empowered to take," said Young, explaining that patients are less likely to adhere to a complicated regimen requiring dozens of pills over the course of a day.

"We know if a patient misses more than 5 percent of the regimen, they are more likely to have an emergence of drug resistance and treatment failure," he said. "There's still tremendous work to do in keeping patients on a 95 percent schedule."

Side effects and toxicity remain challenges as well. And as patients live longer with the disease, new complications have emerged such as displaced body fat deposits and cardiopulmonary changes.

In addition to changing drug combinations and sequences, physicians are working with higher doses of protease inhibitors and experimenting with the concept of a short "drug holiday" to allow patients to recover from the sometimes debilitating effects of the powerful compounds.

Research also continues to assess viral drug resistance as well as to develop other drugs, said Haubrich.

"Sequential therapy is a goal," said Young, calling the idea "almost the New Testament" in AIDS and HIV treatment today. "Implicit in this is that the patient will have a high likelihood of failure on the first therapy."

Future of drug-free AIDS treatment is uncertain
February 4, 1999
New concerns about side effects of AIDS-fighting protease inhibitors
June 30, 1998

Physicians' Research Network
Dr. Richard Haubrich faculty page AIDS information resource
University of California at San Diego
Dr. Benjamin Young information - AIDS
America's Senior Care Pharmacists - HIV/AIDS Pharmacotherapy
University of California at San Diego

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4:30pm ET, 4/16

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