Resistance testing grows more prevalent in U.S.

Society releases testing guidelines

As companies produce faster, cheaper, and more sensitive HIV drug resistance tests, the assays could become an essential part of managing patients, at least in those countries where tests have become available, researchers reported at the 12th World AIDS Conference in Geneva.

"Everyone says we are at the dawn of phenotypic or genotypic assays," John Bartlett, MD, director of the AIDS program at Johns Hopkins University, tells AIDS Alert. "We are not quite there yet, but I think people are going to be using those assays as part of routine monitoring."

Indeed, retrospective studies have confirmed that drug-resistance testing can predict drug failure better than viral-load testing and patient history alone. Prospective studies are under way to validate the findings, said Richard D'Aquila, MD, an AIDS researcher at Harvard Medical School, adding that the tests have improved in the past year but there remain barriers to accessing and interpreting their results quickly and reliably.

The prevalence of drug resistance is expected to increase as more patients experience difficulty complying with combination therapy regimens, researchers warned at the conference. At the same time, there are reports of multidrug-resistant strains of HIV being passed on through sexual contact. Investigators at the University of California at San Francisco reported at the conference on a case in which a patient became infected with a virus resistant to six of the 11 approved antiretroviral drugs.

"We still don't know how frequently resistant strains are transmitted," said Frederick Hecht, MD, assistant clinical professor of medicine at San Francisco General Hospital and lead author of the study. "But we now know that people can acquire strains with multidrug resistance, including resistance to protease inhibitor treatment."

Virologic phenotypic analysis found that the patient's virus was resistant to zidovudine, lamivudine, and four protease inhibitors, he added.

Until now, clinicians have had little guidance on how and when to use resistance testing. In a consensus statement published in June in the Journal of the American Medical Association1 and presented at the conference, the International AIDS Society-USA provides the first official set of principles and guidelines for drug resistance testing. The authors note that resistance testing will be increasingly useful for identifying drugs that are having a suboptimal response. With documentation now of multidrug-resistant strains of HIV being transmitted, the tests also may be considered for antiretroviral drug-naive pregnant women and patients with primary HIV infection in populations where drug resistance is prevalent.

In late July, two new HIV drug-resistance testing procedures will be made available for commercial use in the United States. Laboratory Corporation of America in Burlington, NC, and Virco, a European-based molecular biology company, announced the release of two new diagnostic tests for physicians: LabCorp's Antivirogram and Virco's VircoGEN.

Antivirogram will provide phenotyping, a method of assessing viral sensitivity to HIV drugs by measuring the ability of the virus to grow in the presence of each drug. VircoGEN is a new generation of genotypic testing, which not only identifies genetic mutations that may signify drug resistance but also generates a "virtual phenotype" through its link to Virco's database, according to a LabCorp press release.

Data presented at the conference included a study by researchers in Vancouver showing that patients whose virus was deemed drug-sensitive by phenotypic testing were 12 times more likely to respond to dual protease inhibitor therapy. Patients who had virus classified as "sensitive" by genotypic testing were four times more likely to respond to therapy, say LabCorp officials. The VircoGEN test takes five to 10 days to complete, while the Antivirogram takes three to four weeks, they add.

Reference

1. Hirsch M, Conway B, D'Aquila R, et al. Antiretroviral drug resistance testing in adults with HIV infection. JAMA 1998; 279:1,984-1,991.