A new kind of resistance training - HIV Digest

The rules of the HIV game are constantly being rewritten, which forces researchers and doctors to employ new tools to keep pace. Their latest weapon is drug-resistance testing, which attempts to check the virus' rapid mutation rate.

HIV is adept at generating inexact or mutated copies, which can show resistance to medications. Resistant viral strains can then be transmitted to those newly infected. As many as 49 percent of Americans with HIV are resistant to at least one of the 16 HIV drugs available, according to a study conducted by the University of California at San Diego and the Rand Corp.

Drug-resistance testing clarifies treatment options, since it can ascertain which drugs are poor choices right from the start. It saves time and money, and it cuts health risks associated with medication side effects.

WHICH PATIENTS ARE GOOD CANDIDATES FOR TESTING?

The United States Department of Health and Human Services recommends resistance testing after a treatment fails and for anyone newly infected who hasn't yet begun treatment.

"It's important to know that you can get infected with a virus that's already resistant to several drugs, even though you've never taken them yourself," says Roy Gulick, M.D., director of Cornell University's HIV clinical trials unit. "We don't yet know just how common it is for people to pass resistant HIV strains to each other, but there's concern that, increasingly, people are acquiring resistant viruses."

A person's viral load needs to top 1,000 for resistance testing to be effective, although some laboratories have improved techniques and can now detect strains with loads of 400 to 500, says Gulick. "For those who've failed multiple drug regimens, we repeat the test to see how the current regimen is responding. Some patients have the test done several times a year if they keep turning up resistant."

WHAT KINDS OF TESTS ARE AVAILABLE?

There are two primary types of procedures: genotypic and phenotypic.

Genotypic testing isolates genes from the virus, which are then multiplied and examined for the presence of mutations. Results are compared to a resistance-free virus. Researchers must then interpret a report, linking drugs to mutations known to show resistance. The test costs about $400, and it takes three or four weeks from start to finish.

Phenotypic testing exposes the virus to various drugs to see whether it grows or diminishes. The test is performed in only two commercial laboratories: one in south San Francisco, the other in Belgium. The process, which costs approximately $800, takes from four to eight weeks.

"Most people take the genotypic test first--mostly because of cost and how quickly it comes back," says Gulick. "We don't know the effectiveness of one against the other. Some doctors recommend both."

Gulick adds that there is an "absolute difference" among the quality of genotypic tests, based on which laboratory a blood sample is sent to. "Interpreting results requires extensive knowledge in the field," he says. "Use a reputable lab."

A new test, called "virtual phenotype testing," is actually a genotype test that matches mutations to resistance patterns through a computerized database, taking the guesswork out of interpreting results. The test is "added on" to genotypic testing and costs $50 more, says Gulick.

ARE THERE WAYS TO KEEP HIV FROM BECOMING DRUG-RESISTANT?

Keeping viral levels as low as possible for as long as possible helps avoid mutations from accumulating. When indicated, a potent combination of drugs can keep the virus depressed or even undetectable.

Many drugs have exacting regimens, including dosage levels and times as well as dietary guidelines. When doses are skipped or taken incorrectly, HIV can spawn additional mutations. Drugs can be poorly absorbed if there's diarrhea or vomiting. And one individual may require a higher drug dose than another, depending on gender, height, weight and/or age. All these factors affect mutation occurrence and speed. Arriving at the correct dose, and then following it to the letter, is crucial to reducing the incidence of drug resistance.

IS THE COST OF TESTING COVERED BY INSURANCE?

Most private and public health insurance programs cover the cost of genotypic testing. But not all cover phenotypic testing. A listing of state-by-state insurance coverage can be found at www.aegis.com/ topics/resistance/410.html. For additional information on drug resistance, access www.thebody.com/ treat/resistance.html or www.projectinform.org/ fs/GenoPheno.html

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What to say when your partner doesn't want to use protection

The excuse:

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