International Panel Evaluates Testing For Drug Resistance In HIV

Tests that measure whether the strains of HIV infecting a patient are resistent to antiviral drugs may be useful in helping plan treatment strategies, but more information is needed to determine the best usage of such tests, says an international panel of AIDS experts. In a report appearing in the June 24 issue of the Journal of the American Medical Association, the panel convened by the International AIDS Society-USA outlines several implications of and recommendations regarding testing for drug resistance in HIV. The study's lead author is Martin Hirsch, MD, director of Clincal AIDS Research at the Massachusetts General Hospital and professor of Medicine at Harvard Medical School (HMS).

"It is clear that viral resistance, the existence or development of strains of HIV that can escape the effects of particular antiviral drugs, is an important reason why drug treatment fails some patients," Hirsch says. "While there is not yet enough data available to recommend which of the available tests is best in particular situations, we do believe that resistance information may be useful in guiding treatment, particularly in areas where resistant strains are prevalent."

The panel was made up of 13 physicians from six countries, experts in AIDS treatment and in research relevant to the issue of resistance. The group was convened by the International AIDS Society-USA as part of their effort to monitor and address areas of controversy in the treatment of HIV-related disease. The panel reviewed existing information from published reports, research conference presentations, basic and clinical research studies and information from the manufacturers of available resistance assays and met regularly over a six-month period to develop their report.

Among the group's conclusions are the following:

• Initiation of drug treatment and changes in treatment regimens should be guided by standard measures of the progress of infection--blood tests that measure the levels of HIV or of CD-4 cells, the immune cells primarily targeted by the virus--not by resistance testing.

• Drug resistance is a significant cause, but not the only cause of treatment failure. Other causes that might be considered include the patient's adherence to the treatment regimen, limited drug potency, and differences in how individuals metabolize particular drugs.

• Because viral strains infecting patients may exhibit some drug resistance even before treatment begins, drug regimens that do not totally suppress viral replication will probably lead to the proliferation of resistant strains. Therefore all patients should receive potent combination drug therapy regimens that have the best chance of keeping viral replication at an undetectable level.

• Two types of resistance assays are currently available: genotypic assays that look for known resistance-associated genetic mutations, and phenotypic assays that directly measure whether a particular drug will kill a sample of the virus infecting an individual patient. Each type has certain advantages and disadvantages, but there are insufficient data to recommend one over the other.

• Resistance assays may identify the predominant resistant strains in a patient but miss other resistant strains present in smaller amounts. Also, because previous drug treatment may lead to the survival of resistant strains--even at undetectable levels--interpretation of any resistance assays should also take into account the patient's complete treatment history.

• Although an assay that shows a viral strain may be resistant to a drug should rule out use of that drug, an assay that does not indicate resistance cannot guarantee treatment success.

• Further epidemiological studies are needed to monitor the prevalence of certain resistant strains in particular groups of people or geographic areas. Pretreatment screening for drug resistance may be most useful for groups among whom resistant strains are more prevalent.

"A lot of people are doing resistance testing--and test manufacturers are advocating for their products--but we really haven't known enough about how to interpret or use the information these tests provide," Hirsch says. "This group's guidelines are a start toward better understanding of how resistance tests eventually may help us plan and implement better drug therapy regimens."

Other members of the panel are Brian Conway, MD, of St. Paul's Hospital, Vancouver; Richard D'Aquila, MD, of the MGH; Victoria Johnson, MD, of the University of Alabama at Birmingham School of Medicine; Francoise Brun Vezinet, MD, of Hopital Bichat-Claude Bernard, Paris; Bonaventura Clotet, MD, PhD, of Hospital Universitari Germans Trias i Pujol, Barcelona; Lisa Demeter, MD, University of Rochester; Scott Hammer, MD, Beth Israel Deaconess Medical Center and HMS, Boston; Donna Jacobsen, IAS-USA; Daniel Kuritzkes, MD, University of Colorado Health Sciences Center, Denver; Clive Loveday, MD, PhD, Royal Free Hospital Medical School, London; John Mellors, MD, University of Pittsburgh Medical Center; Stefano Vella, MD, Istituto Superiore di Sanita, Rome; and Douglas Richman, MD, University of California at San Diego. The panel's work was supported by the International AIDS Society-USA, San Francisco.