• The ENVA-3 World Wide Evaluation Study Shows Extensive Differences in Interpretation on HIV-1 Genotype Analysis
  Abstract 1323
  Authored by Annemarie M. J. Wensing (Univ. Med. Ctr., Utrecht, Netherlands), W. Keulen (Univ. Med. Ctr., Utrecht, Netherlands & Virology Networks), M. Buimer (Virology Networks), D. Brambilla (New England Res. Inst., Watertown, MA), R. Schuurman (Univ. Med. Ctr., Utrecht, Netherlands), C. Boucher (Univ. Med. Ctr., Utrecht, Netherlands)
  View the original abstract

This most recent study is from a group that has already done a few studies in the past year to act as a "quality assurance" group for resistance testing. Over the past few years, they have shown some of the limitations in the accuracy of resistance testing; for example, they have shown that labs will come to different conclusions when testing a reference sample containing both sensitive and resistant strains.

In this study, they focused on the interpretation part of testing, asking whether different approaches are more or less accurate when analyzing the importance of any given mutation pattern. As with testing itself, there are multiple approaches to predicting the impact of any mutation pattern; each test has its own interpretation, in addition to the articles and Web-based interpretation systems available.

Here, they sent a reference strain of five samples to a variety of labs, including multiple different commercial labs and labs using different methods of interpretation. They asked the labs to interpret the results, predicting whether the observed mutations would have any impact on the various antivirals, categorizing the results into "active," "partially active" or "inactive." They noted differences of opinion for many of these patterns, including differences for patterns in both RT and protease gene mutations.

Some medications had more agreement, while others were more controversial in understanding the impact of a mutation pattern on its activity. This reflects some of the limitations of our knowledge in understanding the intrinsic activity of medications given differing patterns. In addition, it reflects some of the subtleties in these categories. For example, after a mutation, a drug may show resistance and yet still be active in achieving some reduced degree of suppression. Agreement in describing these changes is clearly something that is an ongoing process so as to ensure that our tests can be used with confidence -- no matter which system is used.

This study is a reminder that both resistance testing, and the expertise in interpreting the results, are needed when making changes in antiviral treatment. These tests have been shown to have a beneficial impact, but the expertise in knowing how to use them is something that many clinicians will also need to have, in order to achieve the best possible results from them.