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Adding New Drugs Keeps HIV Down

Medically Reviewed by Charlotte E. Grayson Mathis, MD
From the WebMD Archives

Aug. 8, 2001 -- It's good news for people taking anti-HIV drugs: When one type of treatment fails to keep the AIDS virus in check, adding two new drugs gets it back under control.

The most pressing challenge in AIDS therapy is what to do when anti-HIV drugs stop working. Once initial therapy fails, doctors often prescribe new drugs. But these so-called salvage therapies rarely work as well or as long as the first treatment. The new study, reported in TheNew England Journal of Medicine, is a first step toward solving this problem.

"We are optimistic" that we have found a way to successfully treat those whose HIV drugs have failed, Mary A. Albrecht, MD, tells WebMD.

So what's the trick?

"We can't treat individuals [whose HIV drugs] are failing by just adding one new drug," their HIV doesn't respond to it, infectious disease expert John W. Mellors, MD, tells WebMD.

But therein lies the catch. Many people with HIV already have taken various drugs, so finding two completely new types of HIV drugs for them to take is very difficult.

Mellors is chief of the division of infectious diseases at the University of Pittsburgh School of Medicine and co-author of an editorial accompanying the Albrecht team's report.

HIV is notorious for developing resistance to any drug thrown at it. That's why people with HIV are given "drug cocktails" that mix several different types of drugs together. The idea is to give the virus such a wallop that it has a much harder time becoming resistant to drugs. Anti-HIV drugs come in three types:

  • Nucleoside analog reverse-transcriptase inhibitors -- or nucs (pronounced "nukes") for short. Nucs shuts off a molecule called reverse transcriptase that HIV needs to live. Six nucs are now available, with two more in human trials.
  • Non-nucleoside reverse transcriptase inhibitors -- or non-nucs. These drugs target reverse transcriptase, too, but they do it in a different way. Three non-nucs are now on the market with others in the pipeline.
  • Protease inhibitors, or PIs. Protease is the enzyme that HIV needs to reproduce so it can infect more cells. PIs jam the works. Six PIs are on the market with more on the way.

In this new study, Albrecht, a researcher at Harvard's Beth Israel Deaconess Medical Center, and co-workers studied 195 people with HIV. All of them had been treated only with nucs, such as AZT, Videx, and Hivid. Most had taken at least two of these drugs for a long time. Though they were doing pretty well most had low -- but not dangerously low -- numbers of immune system cells needed to fight HIV, and HIV levels were rising.

For the new HIV cocktail, the researchers gave all the study participants two nucs -- at least one of which was new to them. They also gave them one of three other HIV treatments: the non-nuc Sustiva, the PI Viracept, or a combination of the two.

After 48 weeks of treatment, those who took the four-drug cocktail had much lower levels of HIV in their blood. The four drugs worked and kept on working for 77% of the patients. Interestingly, just adding Sustiva to the old drug regimen worked longer than adding only Viracept.

"Even in patients who have been maintained for a long time on dual or triple nucleoside therapy, [treatment] can be enhanced by addition of two new classes of drug," Albrecht says.

The study raises many questions. In the U.S. and Europe, almost nobody starts treatment with just nucs any more. If two new classes of drug are needed for effective salvage therapy, what should a patient start with? Is it better to use an all-out approach at first to keep the virus in check? Or is it better to use only two classes at first and save the other two for later? And will new drugs really be there when they are needed?

Mellors says that the answers to these questions rely more on the art than on the science of medicine.

"When the patient is relatively stable and there is no-near term risk of AIDS or death, then we can wait until we have several drugs available -- each from a new class -- to put in a multidrug combination," Mellors says.

But it's usually not that simple. "We are often facing uncertain prognosis and unknown availability. What to do varies from doctor to doctor," says Mellors. "My personal style is to wait until we can get two or three new drugs."

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